Urinary Podocyte Markers nyob rau hauv cov kab mob raum

Yog xav paub ntxiv:ali.ma@wecistanche.com

Lingfeng Zeng, et al

Abstract

Podocytes ua lub luag haujlwm tseem ceeb hauv kev saib xyuas lub raum ua haujlwm, thiab lawv yog qhov tseem ceeb ntawm ntau tusraumkab mob. Kev raug mob Podocyte tau tshwm sim los ntawm kev tso tawm ntawm cov kab mob podocyte-derived cellular fragments thiab podocyte-specific molecular lub hom phiaj rau hauv cov zis, uas tuaj yeem ua haujlwm biomarkers ntawmraumkab mob. Cov podocytes tsis zoo, tsis tuaj yeem siv tau lossis tuag, thiab podocyte-derived microvesicles tuaj yeem txheeb xyuas hauv cov zis los ntawm ntau yam centrifugation, kev pom, thiab kab lis kev cai. Podocyte-specific protein cov hom phiaj los ntawm cov nucleus, cytoplasm, slit-diaphragm, glomerular capillary hauv qab daim nyias nyias, thiab cytoskeleton, nrog rau lawv cov xa xov RNA (mRNA), hauv cov zis, tuaj yeem suav tau los ntawm western blotting, ELISA, lossis quantitative polymer. chain reaction. Txawm hais tias qee qhov ntawm cov txheej txheem no yuav kim lossis siv zog ua haujlwm tam sim no, lawv yuav dhau los ua dav dav rau yav tom ntej vim tias kev txhim kho hauv tshuab thiab automation. Daim ntawv thov ntawmtso zispodocytecov cim rau kev kuaj mob thiab saib xyuas ntawm ntau yamraumkab mobtau tshawb nrhiav tab sis cov ntaub ntawv luam tawm hauv cheeb tsam no tsis txaus thiab tsis muaj kev lees paub sab nraud. Kev tshawb fawb ntxiv yuav tsum tsom mus rau kev tsim qauv, kev sib piv, thiab kev ua haujlwm hauv chav sim, nrog rau kev txhais lawv cov nqi ntxiv rau cov kev kuaj mob niaj hnub.

Ntsiab lus:Podocyte, Biomarker, mRNA, miRNA, Nephrin, Podocin, Podocalyxin, Synaptopodin,Ntevraumkab mob

Cistanche qia tuaj yeem kho mob raum mob

1. Taw qhia

1.1. Epidemiology ntawm kab mob raum mob

Ntevraumkab mob(CKD) yog ib yam kab mob tseem ceeb thiab kim heev [1]. Nrog rau qhov muaj kev kho mob raum, cov kev kho mob siv rau kev kho mob ntawm CKD (Chronicraumkab mob)tau nce siab tom qab xyoo 1960 [2,3]. Hauv 2015, muaj ntau dua 2.5 lab tus neeg mob tau txais kev kho lub raum hloov pauv thoob ntiaj teb, thiab tus lej no tau kwv yees tias yuav nce ob npaug los ntawm 2030 [4]. Cov txiaj ntsig zoo rau kev kuaj mob, kho, thiab saib xyuasraumkab mobxav tau ntau heev.

1.2. Podocyte raws li lub hom phiaj ntawm kab mob raum

Lub luag haujlwm tseem ceeb ntawm lub raum yog kev tshem tawm cov khoom pov tseg hauv cov metabolism thiab cov dej ntau dhau ntawm lub cev [5], uas yog ua tiav los ntawm peb txheej txheem: (1) pom cov ntshav ncig los ntawm glomerulus los tsim ib qho ultrafiltrate hauv Bowman qhov chaw; (2) xaiv reabsorption ntawm cov khoom tseem ceeb ntawm lub raum tubule; thiab (3) xaiv secretion lwm yam metabolic pov tseg los ntawm peritubular capillary mus rau tubular kua [6]

Txawm hais tias lub raum muaj ntau hom xovtooj ntawm tes uas tau teeb tsa hauv qhov muag heev 3- qhov chaw tsim qauv, podocyte ua lub luag haujlwm tseem ceeb hauv kev saib xyuas lub raum ua haujlwm ib txwm muaj thiab yog lub hom phiaj tseem ceeb ntawm ntau tus.raumkab mob. Podocytes yog cov kab mob sib txawv tshwj xeeb uas, ua ke nrog cov hlwb endothelial thiab glomerular capillary hauv qab daus daim nyias nyias (GCBM), ua lub glomerular filtration barrier [7]. Podocytes muaj lub cev voluminous uas yog cais los ntawm GCBM los ntawm qhov chaw sub-podocyte [8]. Lub cev ntawm tes ua rau cov txheej txheem tseem ceeb ntev uas txuas mus rau GCBM thiab tau txuas mus rau tom kawg los ntawm kev nthuav dav ntawm cov txheej txheem ko taw [8].

Podocytes muaj ntau yam kev ua haujlwm ntawm lub cev. Lawv tuav lub glomerular vascular voj morphology, tswj glomerular pom, thiab koom nrog hauv zos immunological thiab inflammatory teb. Tsis tas li ntawd, podocytes yog ib feem lub luag haujlwm rau kev sib txuas thiab kev hloov pauv ntawm GCBM [9], nrog rau kev tsim cov kab mob paracrine xws li vascular endothelial kev loj hlob (VEGF), uas yog ib qho tseem ceeb hauv kev tswj hwm ntawm permeability thiab proliferation ntawm endothelial hlwb. [10]. Podocyte dysfunction plays lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob thiab kev loj hlob ntawm ntau yam.raumkab mob. Kev hloov pauv ntawm ntau yam podocyte-txog cov noob ua rauraumkab mob, uas feem ntau tam sim no kho raws li steroid-resistant nephrotic syndrome thiab histologically li focal glomerulosclerosis (FGS). Ntawm qhov tod tes, tau txais podocyte ua haujlwm tsis zoo, suav nrog kev txo qis ntawm tus lej podocyte lossis qhov ntom ntom thiab fusion ntawm cov txheej txheem podocyte ko taw, ua rau cov txheej txheem endothelial thiab GCBM raug mob, poob ntawm GCBM tsis zoo nqi, Hiatal membrane protein abnormality, thiab thaum kawg proteinuria los ntawm ntau yam mechanisms [ 11, 12] ib.

Ib tug yam ntxwv tshwm sim ntawm kev raug mob podocyte yog qhov tsis muaj zog ntawm kev sib cuam tshuam nrog GCBM, uas sib sau ua ke rau hauv lub detachment ntawm podocytes los ntawm GCBM. Txij li thaum podocytes muaj lub peev xwm tsawg rau kev rov tsim dua tshiab thiab kev ua haujlwm tau zoo, cov podocytes ntxiv tsis tuaj yeem tswj hwm cov khoom siv thiab cov nqi thaiv kev ua haujlwm ntawm GCBM, uas yuav raug puas irreversibly, thiab qhov kawg tshwm sim yog proteinuria [13]. Nyob ntawm qhov hnyav ntawm qhov kev thuam, kev puas tsuaj rau podocytes tuaj yeem ua rau poob ntawm cov txheej txheem ko taw, vacuole thiab pseudocyst tsim, dedifferentiation, thiab apoptosis. Cov qauv nyob sib ze yuav raug cuam tshuam tom qab, suav nrog kev loj hlob ntawm parietal epithelial hlwb, shrinkage ntawm GCBM, poob ntawm glomerular capillary tuff, thiab thaum kawg glomerulosclerosis [14].

1.3. Kev tshuaj xyuas cov ntaub ntawv

Peb tau tshawb xyuas cov ntaub ntawv nrog cov lus tshawb fawb suav nrog "podocyte", "podocyte-associated molecules", lossis "biomarker", ua ke nrog "mob ntevraumkab mob", "mob raum raug mob", "glomerulonephritis", "diabetic nephropathy", lossis "diabeticraumkab mob", tau siv los tshawb nrhiav cov ntaub ntawv cuam tshuam los ntawm Medline, Embase thiab Cochrane Library. Cov ntaub ntawv ntawm cov ntawv tshaj tawm cuam tshuam tau raug tshuaj xyuas rau cov ntaub ntawv muaj peev xwm ntxiv. Cov kev tshawb fawb tsim nyog suav nrog tib neeg thiab tsiaj cov kev tshawb fawb luam tawm ua ntej Lub Xya Hli 2020. Cov ntawv tshaj tawm nrog cov ntsiab lus tsis cuam tshuam, xws li podocyte cell biology, Membrane physiology, thiab molecular manipulation ntawm podocytes, raug cais tawm.

1.4. Podocyte-cov hom phiaj tshwj xeeb ua biomarkers

Kev raug mob Podocyte ua rau kev tso tawm ntawm ntau yam podocyte-derived molecules rau hauv qhov chaw tso zis thiab tuaj yeem ua tus biomarker ntawmraumkab mob(Daim duab 1). Lub cev podocyte tuaj yeem muab faib ua peb qhov sib txawv ntawm lub cev thiab ua haujlwm sib txawv: lub hauv paus ib feem, sab saum toj, thiab cov swb-diaphragm (SD) feem [15]. Cov cell membrane tshwj xeeb muaj nyob hauv txhua qhov, thiab lawv cov kev cuam tshuam nrog cytoplasmic cytoskeleton system yog lub luag haujlwm rau kev ruaj ntseg ntawm podocyte qauv thiab kev ua haujlwm [16]. Qhov loj podocyte-derived molecules uas yog lub hom phiaj rau kev txhim kho biomarker tau sau tseg hauv Table 1.

Fig. 1. Kev raug mob Podocyte thiab tej zaum cov cim podocyte-derived hauv cov zis. Kev raug mob rau podocytes ua rau muaj 3 txoj kev cuam tshuam txog kev cuam tshuam ntawm pathological: hloov morphological, apoptosis, thiab detachment. Podocytes yuav nyob twj ywm tab sis tshwm sim raws li kev hloov pauv ntawm morphological uas muaj qhov cuam tshuam rau hauv qab, xws li proteinuria thiab tubulointerstitial fibrosis. Podocyte apoptosis tuaj yeem tshwm sim los ntawm kev hloov pauv morphological lossis ncaj qha los ntawm kev thuam tshwj xeeb. Kev poob ntawm podocytes hauv glomeruli (piv txwv li podocytopenia) ua rau kev hloov pauv ntawm cov kab ke glomerular capillary thiab ua rau glomerulosclerosis. Podocytes, yog apoptotic los yog siv tau vim poob ntawm 3 1 integrin, tuaj yeem tshem tawm mus rau qhov chaw tso zis, raug txheeb xyuas hauv cov zis, thiab ua cov cim ntawmraumkab mob. Cov vesicles, microparticles, los yog podocyte-specific molecules muab tau los ntawm raug mob los yog apoptotic podocytes kuj raug kuaj pom nyob rau hauv cov zis thiab ua hauj lwm raws li biomarkers. (GCBM, glomerular capillary hauv qab daim nyias nyias; AgII, angiotensin II; TGF-, transforming kev loj hlob factor-beta; ROS, reactive oxygen hom).

1.5. Nuclear thiab cytoplasmic lub hom phiaj

Wilms ' qog suppressor gene -1 (WT1) yog zinc ntiv tes zoo li cov ntaub ntawv hloov pauv hauv cov podocyte nucleus thiab tej zaum yog qhov feem ntau siv podocyte-cov cim tshwj xeeb rau kev tshawb fawb histological [17]. WT1 noob muaj 10 exons, uas exons 7 txog 10 encode 4 zinc ntiv tes ntawm DNA-binding domain. WT1 tau qhia tshwj xeeb hauv podocytes thiab nws tej zaum yuav tswj cov kev qhia ntawm nephrin [18]. Heterozygous kev hloov pauv hauv exons 8 thiab 9 ntawm WT1 noob ua rau Denys-Drash syndrome, uas tshwm sim nrog nephrotic syndrome, txiv neej pseudohermaphroditism, thiab Wilms qog [19].

Lwm cov nuclear thiab cytoplasmic proteins ntawm podocytes tsis tau kawm zoo li biomarkers. AarF domain-muaj kinase-4 (ADCK4) tshwj xeeb yog tam sim no nyob rau hauv mitochondria nyob rau hauv cov txheej txheem ko taw ntawm nas podocytes [20]. ADCK4 yog lub luag haujlwm rau stabilizing CoQ complex thiab nws yuav tsum tau rau ib txwm podocyte homeostasis muaj nuj nqi [20]. Podocyte-specific ADCK4 ablation hauv cov nas ua rau cov txheej txheem ko taw effacement, disorganization ntawm cov filtration slit, loj thiab dysfunctional mitochondria, thiab txo CoQ10 [21], thiab kev kho mob rov qab CoQ10, mitochondrial muaj nuj nqi, txhim kho podocytes tiv thaiv footment2 txheej txheem, , 22] ib.

1.6. Slit-diaphragm protein complex

Proteins Cheebtsam ntawm podocyte slit-diaphragm tau kawm ntau yam raws li biomarkers ntawmraumkab mob. Cov proteins loj hauv pawg no suav nrog nephrin, podocin, CD2-cov protein sib txuas (CD2AP), thiab podoplanin [23]. Nephrin yog transmembrane protein nrog extracellular domains uas tsim lub hauv paus ntawm lub diaphragm slit. Nws ua ob qho tib si raws li lub cev sieve barrier thiab lub teeb liab scaffold [24]. Kev hloov pauv ntawm cov noob nephrin yog thawj zaug tshaj tawm ua rau lub cev xeeb tub nephrotic syndrome hauv tib neeg [25]. Podocin thiab CD2AP yog lub luag haujlwm rau kev txuas nephrin mus rau actin cytoskeleton hauv qab cell membrane. Podocin yog cov protein zoo li cov plaub hau ntawm tsev neeg stomatin thiab tsuas yog qhia hauv podocytes [26]. Nws yog encoded los ntawm NPHS2 noob uas muaj yim exons thiab nyob rau ntawm chromosome 1q25-q31 cheeb tsam [27]. Kev hloov pauv ntawm NPHS2 noob ua rau autosomal recessive steroid-resistant nephrotic syndrome nyob rau hauv ob qho tib si menyuam yaus thiab cov neeg laus [27,28]. CD2AP yog scaffolding molecule uas ncaj qha cuam tshuam nrog filamentous actin thiab lwm cov cell membrane proteins thiab cuam tshuam rau hauv dynamic actin remodeling thiab membrane trafficking [29]. Podoplanin yog ib qho me me transmembrane glycoprotein nrog ntau O-glycoside chains. Kev xaiv poob ntawm podoplanin hauv podocytes ua rau muaj proteinuria, ua raws li kev hloov pauv hauv podocyte morphology hauv cov qauv nas ntawm cov proteinuria [30].

Cistance yog qhov zoo rau lub raum

1.7. Cov hom phiaj txuas rau GCBM

Cov protein tseem ceeb ntawm thaj av podocyte basal yog cov 3 1 integrin thiab -dystroglycan (-DG). Cov proteins no thauj khoom podocytes mus rau GCBM thiab ua lub luag haujlwm tseem ceeb hauv kev tswj xyuas qhov tseeb ntawm podocyte nrog rau kev ncaj ncees ntawm cov ntaub ntawv pom [31,32]. Lub 3 1 integrin yog ib qho transmembrane protein nrog lub extracellular domain txuas mus rau laminin G-zoo li domain G (LG) ntawm laminin 521 hauv GCBM, thaum nws cheeb tsam cytoplasmic txuas nrog podocyte cytoskeleton los ntawm -actinin {{ 9}} ib. Cov glycosylated protein -DG txuas nrog lub cytoskeleton ntawm utrophin, thiab mus rau podocyte thiab GCBM los ntawm nws kev cuam tshuam nrog laminin 521.

1.8. Lub hom phiaj ntawm daim nyias nyias

Podocalyxin yog cov protein loj transmembrane nyob rau sab apical ntawm podocyte. Nws yog ib qho tsis zoo them nyiaj sialic acid protein uas ua rau muaj qhov cuam tshuam ntawm glomerular pom [33]. Podocalyxin muaj peb lub luag haujlwm: (1) tiv thaiv cov protein tsis zoo los ntawm kev xau mus rau hauv cov zis; (2) tswj kev sib cais ntawm podocytes uas nyob ib sab; thiab (3) los tiv thaiv adhesion ntawm epithelial hlwb thiab capillary loops [34]. Podocalyxin txuas nrog actin cytoskeleton los ntawm ezrin thiab sodium-proton exchanger regulatory factor 2 (NHERF2).

1.9. Cov hom phiaj ntsig txog Actin

Ib tug xov tooj ntawm podocyte-specific proteins yog txuas mus rau actin cytoskeleton thiab tuav lub 3-dimensional qauv ntawm lub podocyte. Cov hom phiaj kawm zoo tshaj plaws ntawm pab pawg no yog synaptopodin thiab -actinin-4. Ob leeg khi rau cov pob txha actin los ntawm kev cuam tshuam nrog cov membrane-sociated guanylate kinase nrog inverted orientation -1 (MAGI-1) [35]. Synaptopodin yog proline-nplua nuj linear protein encoded los ntawm SYNPO noob [36] thiab tau qhia nyob rau hauv txawv podocytes thaum lawv tsim cov txheej txheem ko taw. Yog li ntawd, synaptopodin raug suav hais tias yog ib qho cim ntawm cov laus podocytes [37].

2. Txoj kev kawm

2.1. Intra-glomerular podocyte markers

Txawm hais tias lub hom phiaj ntawm qhov kev tshuaj xyuas no yog nyob rautso zispodocytecov cim, nws yog qhov tsim nyog los tham luv luv txog kev tshawb pom cov cim hauv lub raum. Podocyte depletion tuaj yeem yog qhov tseeb (poob ntawm podocytes) lossis txheeb ze (txo cov podocytes ib ntim ntawm glomerulus) [38]. Cov txheej txheem kub ntawm kev suav cov podocytes hauv ob lub raum yog cov txheej txheem stereological (lub teeb lossis electron microscopes, confocal laser scanning microscopes, ultrasound, xam tomography, lossis magnetic resonance imaging) [39]. Txawm li cas los xij, txhua tus ntawm lawv yog lub sijhawm siv sijhawm thiab siv zog ua haujlwm. Tsis ntev los no, Venkatareddy et al. Kev ntsuas tus qauv rau kev kwv yees ntawm podocyte ceev los ntawm ib qho paraffin-embedded formalin-taw seem, nyob rau hauv uas podocyte nuclei tau pom los ntawm indirect immunofluorescence nrog cov tshuaj tiv thaiv tiv thaiv WT1 los yog transducin-zoo li enhancer ntawm phua [40]. Ib txoj kev tshawb fawb tom qab tau pom tias txoj kev no tau muab qhov tseeb podocyte enumeration nyob rau hauv tus qauv transgenic nas ntawm kev xaiv podocyte depletion, lees paub tias txoj hauv kev no muab cov cuab yeej muaj txiaj ntsig zoo rau kev tshuaj xyuas ntawm podocyte depletion hauv tag nrho glomeruli [41]. Txawm li cas los xij, txoj kev no tseem yuav tsum tau kuaj lub raum biopsy thiab yog li tsis tsim nyog rau kev soj ntsuam serial.

2.2. Cov zis podocyte kom muaj nuj nqis thiab kab lis kev cai

Txij li thaum podocytes raug kho rau lawv txoj haujlwm physiological nkaus xwb los ntawm cov txheej txheem ko taw, lawv muaj peev xwm ua rau poob raws li cov hlwb siv tau hauv cov zis [42]. Qhov tseeb, cov podocytes tsis zoo tuaj yeem pom hauv cov zis ntawm cov neeg noj qab haus huv thiab cov neeg mobraumkab mob[43], thiab tso zis tsis tuaj yeem yog qhov tseem ceeb ntawm kev ua haujlwm ntawm podocytes depletion thaum lub sij hawm kev loj hlob ntawm CKD(Chronicraumkab mob)[42]. Cov txheej txheem ib txwm siv rau kev txheeb xyuas cov podocytes hauv cov zis suav nrog cytospin cov tswv yim thiab kev tshawb fawb immunofluorescence nrog tshwj xeeb cov tshuaj tiv thaiv podocalyxin antibodies [44], uas automation yog ib feem ua tau. Txawm li cas los xij, cov txheej txheem tau txwv tsis pub nkag siab thiab tshwj xeeb vim tias muaj cov kab mob sib kis ntawm cov khib nyiab hauv cov zis tso zis.

Xwb, podocytes tuaj yeem txheeb xyuas los ntawm kev tshawb pom ntawm podocyte-specific tryptic peptides nrog kua chromatography ua ke nrog tandem mass spectrometry (LC-MS / MS). Txawm hais tias cov cuab yeej siv tus nqi ntawm cov txheej txheem no yog siab, nws muaj qhov zoo ntawm kev ua tus neeg teb xov tooj-ywj siab thiab muaj peev xwm ua tau zoo heev [45], thiab tej zaum yuav muaj kev siv ntau ntxiv hauv kev soj ntsuam kuaj mob.

Cov kev tshawb fawb yav dhau los tau qhia tias nrog cov txheej txheem cytospin immunofluorescence, cov neeg noj qab haus huv tso tawm tsawg dua 0.5 podocytes / mg creatinine, thaum cov neeg mob uas muaj kab mob glomerular tso tawm mus txog 400 podocytes / mg creatinine [43]. Feem ntau ntawmtso zispodocytesyog siv tau thaum kuaj nrog propidium iodide cais tawm thiab TUNEL staining [43]. Hauv txoj kev xav, kab lis kev cai ntawm podocytes ex vivo yuav yog li ntawd txhim kho qhov tshwj xeeb ntawm kev txheeb xyuas podocyte los ntawm kev tshem tawm cov hlwb tuag thiab tsis muaj tseeb. Txawm li cas los xij, podocytes tsis nquag proliferate hauv vivo, thiab cov kev sim tshwj xeeb yog xav tau rau lawv cov kab lis kev cai ex vivo [46]. Cov ntaub ntawv dhau los tau qhia tias podocytes tuaj yeem ua ntej loj hlob nyob rau hauv txoj kev loj hlob-tso cai, qhov twg immortalized podocytes replicate [46]. Cov xov xwm kab lis kev cai ntawm tes rau lub hom phiaj no feem ntau muaj Roswell Park Memorial Institute (RPMI) 1640 los yog Dulbecco's modified Eagle's nruab nrab, nrog 10 feem pua ​​​​fetal bovine serum ntxiv nrog 20-100 U / ml ntawm nas interferon-gamma (INF-), thiab kab lis kev cai tais diav feem ntau coated nrog hom I collagen los txhawb podocyte proliferation [46]. Txoj kev no muaj txiaj ntsig zoo hauv kev kawm txhais lus thiab kho lub hom phiaj kev txheeb xyuas tab sis nyuaj heev rau kev siv tshuaj kho mob niaj hnub.

Cistanche tuaj yeem txhim kho lub raum ua haujlwm

2.3. Tso zis podocyte-derived fragments

Extracellular vesicles (EVs) yog kheej kheej membranous lub cev tso tawm los ntawm ntau hom cell [47]. Nyob rau hauv cov zis, EVs uas muaj apical membrane thiab intracellular kua yog los ntawm tag nrho cov nephron segments, xws li podocytes, lub raum tubular epithelial hlwb, thiab uroepithelial hlwb mus rau hauv cov zis. Urinary EVs muaj cov cim qhia txog kev ua haujlwm tsis zoo thiab kev raug mob ntawm lub raum. Cov kev tshawb fawb tsis ntev los no qhia ntxiv tias EVs tuaj yeem cuam tshuam rau kev sib txuas lus sib txuas lus [48]. Tsis tas li ntawd, cov kev tshawb fawb yav dhau los kuj tau pom tias cov apical cell membranes tawg los ntawm cov raug mob podocytes mus rau hauv cov zis [49], thiab tuaj yeem txheeb xyuas tau tias yog cov qauv podocalyxin-positive granular (PPGS) los ntawm electron microscopy [49]. Hauv cov qauv nas mob ntshav qab zib, cov zis exosomes los ntawm podocytes tuaj yeem raug cais tawm los ntawm serial centrifugation, thiab microparticles tuaj yeem ua kom muaj nuj nqis los ntawm kev ntws cytometry siv annexin V antibody (uas kuaj pom tag nrho cov microparticles), tom qab los ntawm cov tshuaj tiv thaiv rau podocalyxin lossis podoplanin (uas tshwj xeeb tshaj tawm cov tshuaj tiv thaiv kab mob) [50,51]. Kev tsom xam ntxiv lub teeb-scattering tuaj yeem siv los txiav txim siab qhov loj ntawm microparticles [52]. Nrog rau cov kev txawj ntse no, nws tau pom tias podocyte-derived microparticles tau nce hauv cov nas thaum raug cov piam thaj siab [51], nrog rau cov nas mob ntshav qab zib ua ntej pib ntawm albuminuria [52]. Nyob rau hauv rooj plaub qub, qhov txawv txav tau raug txwv los ntawm Rho-kinase inhibitor, qhia tias cytoskeletal reorganization yog qhov tseem ceeb ntawm kev tso tawm microparticle [51]. Txawm li cas los xij, kev siv cov txheej txheem no rau tib neegraumkab mobtsis tau tshawb nrhiav.

Tsis yog ntsuas tus naj npawb thiab qhov loj ntawm podocyte-derived EVs thiab microparticles hauv cov zis, tsis ntev los no muaj kev txaus siab loj hlob hauv kev ntsuas podocyte tshwj xeeb molecules hauv cov zis exosomes. Piv txwv li, podocyte-derived signal transduction yam (PDSTFs) hauv cov zis EVs tau raug npaj los ua tus neeg sib tw muaj peev xwm rau kev soj ntsuam ntawm kev raug mob podocyte [52]. Txawm li cas los xij, lawv daim ntawv thov kev kho mob tseem nyob hauv kev txhim kho.

2.4. Lub hom phiaj ntawm cov zis podocyte-cov protein tshwj xeeb

Cov theem tso zis ntawm ob peb lub hom phiaj podocyte tshwj xeeb yog ntsuas tau yooj yim thiab lawv lub luag haujlwm ua biomarkers ntawmraumkab mobtau kawm. Cov theem ntawm cov zis podocalyxin tuaj yeem ntsuas tau los ntawm kev tsis ncaj qha immunofluorescence, ELISA, lossis ntws cytometry [53], thiab tau thov ua tus cim rautso zispodocytesuav. Txawm li cas los xij, ib txoj kev tshawb fawb yav dhau los tau pom tias cov zis podocalyxin feem ntau yog los ntawm cov kab mob apical ntawm cov neeg raug mob podocytes es tsis yog cov uas tsis zoo raug muab tso rau hauv cov zis, thiab nws qib tau nce rau hauv lub raum thaum ntxov [49]. Podocalyxin thiab nephrin, lwm qhov tseem ceeb ntawm podocyte-specific protein lub hom phiaj hauv cov zis, tsis tuaj yeem kuaj pom hauv cov zis ntawm cov neeg noj qab haus huv los ntawm Western blotting [54] tab sis tuaj yeem pom tau los ntawm cov pa ELISA hauv cov neeg mob pre-eclampsia [55]. Ntxiv mus, urinary nephrin qib cuam tshuam nrog qhov hnyav ntawm proteinuria [56] thiab lub raum ua haujlwm [57]. Plasma nephrin theem kuj tuaj yeem ntsuas [57], tab sis nws tsis raug txiav txim siab txog kev lom neeg lossis kev kho mob. Qhov teeb meem loj ntawm kev siv cov zis theem ntawm podocyte-specific protein cov hom phiaj raws li kev kho mob biomarker yog qhov tsis tshua muaj siab (feem ntau nyob rau hauv qhov ntau ntawm ng / ml) thiab cov nyhuv confounding ntawm cov zis concentration-dilution.

2.5. Tso zis podocyte-specific mRNAs

Kev ntsuas ntawmtso zispodocyte-specific mRNA qib tau raug npaj ua lwm txoj hauv kev rau kev txiav txim siab ntawm cov zis podocyte suav. Tus nqi ntawm podocyte-specific mRNA hauv cov zis feem ntau tsis txaus rau txoj kev tshawb fawb sab qaum teb ib txwm muaj tab sis tau yooj yim ntsuas los ntawm lub sij hawm muaj nuj nqis polymerase saw cov tshuaj tiv thaiv (RT-QPCR). Ob qhov kev tshawb fawb yav dhau los tau pom tias cov zis nephrin mRNA qib muaj kev sib raug zoo nrog cov zis podocyte suav [56,58]. Nyob rau hauv tus nas qauv ntawm anti-glomerular qab daus daim nyias nyias kab mob nrog ib tug serial raum biopsy,tso zispodocyte-specific mRNA qib correlated nrog tus nqi ntawm glomerular podocyte poob [52].

Cov kev tshawb fawb tsis ntev los no, txawm li cas los xij, tau hloov qhov kev tsom mus rau cov zis mRNA cov ntsuas ntsuas raws li tus lej cim rau kev ntxhov siab ntawm podocyte lossis txheeb ze raug mob podocyte. Hauv cov qauv nas, cov kab mob glomerular zuj zus tau cuam tshuam nrog kev txo qis nephrin piv rau podocin mRNA qib, thiab tso zis podocin-rau-nephrin mRNA piv nrog rau qhov hnyav ntawm histological kev loj hlob [59]. Hauv kev tshawb fawb tom qab, qhov nruab nrab ntawm cov hlab ntsha siab ntawm cov neeg noj qab haus huv tau pom tias muaj feem cuam tshuam nrog cov zis podocin mRNA rau creatinine piv (ib qho cim ntawm podocyte detachment), podocin-rau-nephrin mRNA piv (ib qho cim ntawm kev ntxhov siab ntawm podocyte), thiab tso zis podocin. -to-aquaporin-2 mRNA ratio (tus cim ntawm tus txheeb ze podocyte raug mob piv rau tubular raug mob) [60]. Kev raug mob Glomerular tshwj xeeb yog txuam nrog nce zis podocin-to-aquaporin-2 thiab nephrin-to-aquaporin-2 mRNA ratios [61].

2.6. MiRNA cov cim qhia tshwj xeeb rau podocytes

Micro-RNAs (miRNAs) yog luv luv tsis-coding RNAs uas tswj ntau txoj hauv kev lom neeg los ntawm kev tsom rau mRNAs [62]. Zoo ib yam li mRNA, urinary miRNA yog nkag tau los ntawm RT-qPCR [63]. Los ntawm qhov kev xav ntawm biomarker txoj kev loj hlob, miRNA muaj qhov zoo ntawm kev tiv thaiv kom tsis txhob degradation, uas pab txhawb nws txoj kev kho mob nrog rau kev kawm ntawm cov qauv archive [63]. Ntau qhov kev hloov pauv miRNA tshwj xeeb tau pom hauvraumkab mob[9]. Piv txwv li, podocyte-specific poob ntawm kev ua haujlwm miRNAs, suav nrog miR-23b, miR-24, thiab miR-26a, tau pom tias ua rau glomerular thiab tubular raug mob [64]. Tshwj xeeb, miR-27b tswj kev muaj sia nyob ntawm podocyte los ntawm kev tsom adenosine receptor 2B [65]. Ib yam li ntawd, urinary miR-21, miR-124, thiab miR{11}} theem tau raug tshaj tawm tias muaj feem cuam tshuam nrog rau qhov hnyav ntawm lub raum tsis ua haujlwm (albuminuria thiab kwv yees GFR) thiabtso zispodocyteCov cim (nephrin, synaptopodin, thiab podocalyxin) hauv cov neeg mob ntshav qab zib [66]. Cov kev tshawb fawb tsis ntev los no tau txheeb xyuas cov kab hauv qab tshwj xeeb rau ntau lub miRNAs uas yuav cuam tshuam rau cov kab mob lossis kev loj hlob ntawmraumkab mob. Tshwj xeeb tshaj yog, miR-193ib qho kev tawm tsam ntawm WT- 1, uas cuam tshuam rau kev sib txawv ntawm cov podocyte [67] thiab tuaj yeem ua lub luag haujlwm hauv kev tsim cov kab mob glomerular [68]. Ntawm qhov tod tes, miR-21 inhibits qhov kev qhia ntawm cov ntaub so ntswg inhibitor ntawm metalloproteinase 3 (TIMP3) [69,70], miR-26ib qho inhibits kev loj hlob ntawm beta-1 (TGF{{ 11}}) qhia [71,72], miR-23b hom phiaj Ras GTPase-activating protein SH3 domain-binding protein 2 (G3BP2) [73], miR-29c hom phiaj Sprouty homolog 1 (Spry1 [74]; ib. Tag nrho cov no koom nrog hauv kev nce qib ntawm ntshav qab zib nephropathy.

Cistanche rau kev txhim kho raum ua haujlwm

Txawm li cas los xij, podocyte txhawb nqa tsuas yog ib feem me me ntawm cov zis miRNA. Ib qho kev hloov pauv miRNA tshwj xeeb pom hauv cov podocytes yuav tsis tuaj yeem pom hauv cov zis, thaum muaj kev hloov pauv hauv cov zis miRNA tuaj yeem cuam tshuam cov kev hloov pauv hauv lwm hom ntawm lub raum [75,76]. Piv txwv li, txawm hais tias cov zis ntawm miR-155, miR-663, thiab miR-1915 yog qhov sib txawv ntawm cov neeg mob uas muaj FGS lossis kev hloov pauv nephropathy (MCN) thiab tswj kev noj qab haus huv [77], nws tsis tau pom tias miR-155, miR-663, lossis miR-1915 tshwj xeeb yog los ntawm podocytes. Kev sib raug zoo tseem ceeb ntawm ntau qib miRNA thiab cov cim kev raug mob ntawm tubular, suav nrog qib zis ntawm N-acetyl- -D-glucosaminidase (NAG) thiab lub raum raug mob molecule-1 (KIM-1) [66], kuj tau tshaj tawm. Hauv lwm lo lus, nws tsis yooj yim rau kev lees paub lawv qhov tshwj xeeb raws li cov cim kev raug mob podocyte. Qhov tshwj xeeb tshwj xeeb rau txoj cai no yog miR-26a. Ib txoj kev tshawb fawb tsis ntev los no tau pom tias cov urinary exosomal miR-26ib qib tau nce siab dua hauv lupus nephritis dua li kev tswj hwm kev noj qab haus huv, miR-26a yog qhov ntau tshaj plaws qhia miRNA hauv glomerulus ntawm ib txwm C57BL/6 nas, thiab miR-26a yog lub luag haujlwm rau kev tswj hwm ntawm podocyte sib txawv thiab cytoskeletal kev ncaj ncees [78]. Txawm li cas los xij, lub luag haujlwm ntawm urinary miR-26a raws li cov cim qhia tshwj xeeb ntawm podocyte yuav tsum tau lees paub.

2.7. Circulating podocyte markers

Ntau yam ntawm cov cim podocyte tau hais saum toj no, tshwj xeeb tshaj yog cov hom phiaj ntawm cov protein tshwj xeeb thiab mRNAs, tuaj yeem ntsuas hauv cov kab ke hauv lub cev [56,79,80], thiab lawv cov qib plasma raws li biomarker ntawmraumkab mobtau tshawb nrhiav [55,81–84]. Txawm li cas los xij, kev sib tham tag nrho ntawm lub ncauj lus no dhau ntawm qhov kev tshuaj xyuas no. Cov txiaj ntsig tseem ceeb thiab qhov tsis zoo ntawm cov txheej txheem saum toj no tau piav qhia hauv Table 2.

3. Tso zis podocyte cim nyob rau hauv tej kab mob raum

3.1. Mob raum mob ntshav qab zib

Mob ntshav qab zibraumkab mob(DKD) yog feem ntau ua rau CKD(Chronicraumkab mob)nyob ib ncig ntawm lub ntiaj teb no, thiab muaj ntau yam ntaub ntawv ntawm kev siv ntau yamtso zispodocyteCov cim rau kev kuaj mob thiab saib xyuas DKD. Piv txwv li, Jim et al [14] tau tshaj tawm tias urinary nephrin qib tau kuaj pom hauv txhua tus neeg mob DKD uas muaj albuminuria, tab sis tsuas yog 54 feem pua ​​​​ntawm cov tsis muaj albuminuria. Cov qib nephrin nyob rau hauv cov zis sib cuam tshuam nrog qib ntawm albuminuria, thiab inversely nrog raum ua haujlwm [14]. Ma et al tau tshaj tawm tias cov zis angiopoietin-zoo li-4 (Angptl4) qib tau nce hauv DKD [85]. Cov zis podocalyxin qib tau nce ntxiv hauv cov neeg mob ntshav qab zib ua ntej qhov pib ntawm microalbuminuria thiab tej zaum yuav nkag siab ntau dua li microalbuminuria rau kev tshawb pom ntxov ntawm DKD [86]. Hauv kev tsim DKD, cov zis podocalyxin qib zoo sib raug zoo nrog qib HbA1c thiab albumin-to-creatinine piv [87,88]. Muab ua ke, cov txiaj ntsig muaj qhia tau hais tias qib zis ntawm ob peb lub hom phiaj podocyte tshwj xeeb yog cov cim thaum ntxov ntawm DKD, thiab qib podocalyxin tso zis yog qhov cim tseem ceeb tshaj plaws hauv qhov no [54].

Cov theem ntawm lub hom phiaj ntawm podocyte tshwj xeeb hauv cov zis ib leeg kuj tau tshawb nrhiav.tso zispodocyteCov qib microparticle, raws li kev txiav txim siab los ntawm kev khiav cytometry, tau siab dua hauv hom 1 ntshav qab zib ntau dua li kev tswj hwm kev noj qab haus huv, thiab qib ntxiv ntxiv nrog hyperglycemic clamp [89]. Urinary exosomal WT-1 qib cuam tshuam nrog qhov hnyav ntawm cov proteinuria, lub raum ua haujlwm, glomerular puas, thiab tus nqi ntawm lub raum ua haujlwm poob qis hauv cov neeg mob ntshav qab zib [58,90]. Hauv lwm txoj kev tshawb fawb, glycogen synthase kinase (GSK) 3 qib hauv cov zis tawm ntawm lub cev tau raug ntau dua li albuminuria hauv kev cais cov neeg mob ntshav qab zib nrog thiab tsis muaj lub raum tsis zoo [91]. Txawm li cas los xij, cov txheej txheem ntawm qhov kev ntsuam xyuas no yog qhov nyuaj thiab yuav tsis siv tau rau kev xyaum kho mob niaj hnub.

Raws li podocyte-specific mRNA cov cim hauv cov zis, kev tshawb fawb yav dhau los tau pom tias cov zis mRNA qib ntawm nephrin, podocin, synaptopodin, WT-1, thiab -actin-4 tau siab dua hauv cov neeg mob DKD dua li kev tswj hwm ib txwm muaj. [92]. Muaj qhov sib txawv tseem ceeb hauv cov zis mRNA qib ntawm nephrin, podocin, -actinin-4, thiab CD2-sociated protein nyob rau hauv cov neeg mob ntshav qab zib uas muaj ntau yam mob ntawm albuminuria [93]. urinary mRNA theem ntawm nephrin, podocin, synaptopodin, WT-1, thiab -actin{11}} kuj cuam tshuam nrogtso zispodocytesuav, qib urinary nephrin, albuminuria, thiab qhov hnyav ntawm lub raum tsis zoo [93]. Tsis ntev los no, urinary podocyte-specific mRNA qib tau pom ua ntej qhov pib ntawm microalbuminuria hauv cov neeg mob ntshav qab zib hom 2 [94], thiab cov zis podocin mRNA-rau-creatinine piv, ib qho cim ntawm podocyte detachment, cuam tshuam nrog tus nqi tom ntej. Lub raum tsis ua haujlwm [94] Tsis tas li ntawd, urinary synaptopodin mRNA qib qis dua tom qab 12 lub lis piam ntawm angiotensin-hloov enzyme (ACE) inhibitor thiab angiotensin receptor blocker (ARB) kev sib xyaw ua ke nrog kev kho mob piv rau ACE inhibitor monotherapy [95]. Muab ua ke, muaj pov thawj qhia tias kev ntsuas ntawm podocyte-specific mRNA qib hauv cov zis yuav muaj txiaj ntsig rau kev pheej hmoo stratification thiab saib xyuas cov lus teb kho mob hauv DKD.

3.2. Kev hloov pauv tsawg kawg hauv nephropathy thiab focal glomerulosclerosis

MCN thiab FGS feem ntau suav tias yog kab mob podocyte, thiab lub luag haujlwm ntawmtso zispodocytecov hom phiaj tau raug sim. Zhou et al. [96] tau tshaj tawm tias urinary exosomal WT-1 qib, raws li ntsuas los ntawm cov txheej txheem immunoblotting, tau nce siab hauv cov neeg mob FGS ntau dua li cov neeg mob steroid-sensitive nephrotic syndrome (SSNS) lossis cov neeg ua haujlwm noj qab haus huv. Urinary exosomal WT-1 qib tau txo qis tom qab kho corticosteroid thiab tshem tawm ntawm FGS lossis SSNS [96]. Hauv lwm txoj kev tshawb fawb, qib urinary nephrin, raws li ntsuas los ntawm ib qho kev ntsuam xyuas ELISA, tau nce siab dua rau cov neeg laus nrog FGS dua li lwm yam ua rau nephrotic syndrome [97].

Cov theem zis ntawm podocyte-specific mRNA kuj tau kawm. Ib txoj kev tshawb fawb thaum ntxov tau pom tias cov urinary nephrin thiab podocin mRNA qib tsis sib txawv ntawm cov neeg mob MCN thiab cov neeg ua haujlwm noj qab haus huv, thiab lawv cov qib tau qis dua cov neeg mob DKD [98]. Kev tshawb fawb tom qab tau pom tias cov zis nephrin thiab podocin mRNA qib qis dua hauv cov neeg mob MCN dua li hauv FGS lossis kev tswj hwm kev noj qab haus huv, thiab qhov loj ntawm kev txo qis cuam tshuam nrog qib proteinuria [99]. Nyob rau hauv txoj kev tshawb no, urinary synaptopodin mRNA qib tau pom tias muaj feem cuam tshuam nrog rau lub raum ua haujlwm poob qis hauv FGS cov neeg mob [99], qhia tias qhov kev hloov pauv zoo hauv FGS podocytes tuaj yeem txheeb xyuas hauv cov zis.

3.3. Membranous nephropathy

Txawm hais tias qhov tseem ceeb ntawm kev hloov pauv ntawm membranous nephropathy (MGN) yog qhov tso tawm ntawm lub cev tiv thaiv kab mob hauv qhov chaw subepithelial, uas ua rau muaj kev hloov pauv ntawm glomerular filtration barrier, kev tshawb fawb ntawmtso zispodocyteCov cim hauv MGN tsis tshua muaj. Cov urinary sediment mRNA qib ntawm nephrin, podocin, thiab synaptopodin tau nce siab hauv MGN, tab sis cov qib tau sib txawv MGN ntseeg tau los ntawm lwm yam ua rau nephrotic syndrome [98]. Tsis ntev los no, Lu li al [100] qhia tias tus naj npawb ntawmtso zispodocyte-derived microparticles txo qis ib txhij nrog kev txhim kho hauv kev kho mob tsis zoo tom qab kev siv tshuaj tiv thaiv kab mob, qhia txog lub luag haujlwm hauv kev saib xyuas MGN.

3.4. IgA nephropathy

Txawm hais tias immunoglobulin A nephropathy (IgAN) feem ntau yog kab mob mesangial, lub luag haujlwm ntawmtso zispodocytesuav raws li biomarker tau tshawb nrhiav. Qhov tseem ceeb, Shen et al [101] pom tias cov neeg mob IgAN muaj qhov nce hauv cov zis podocyte poob, tsawg dua podocytes hauv glomeruli, thiab cov txheej txheem ko taw hnyav dua hauv cov qog nqaij hlav hauv lub raum. Hauv txoj kev tshawb no, urinary podocyte tau txheeb xyuas los ntawm kev tsis ncaj qha immunofluorescence kawm ntawm podocalyxin, thiabtso zispodocytesuav correlated nrog serum creatinine thiab proteinuria [101]. Ib txoj kev tshawb fawb tom qab tau pom tias cov zis podocytes hauv IgAN cov neeg mob uas muaj segmental sclerosis yog siab dua li cov uas tsis muaj segmental sclerosis [102]. Hauv cov menyuam yaus uas muaj IgAN lossis Henoch-Sch¨ online purpura nephritis, Hara et al [103] tau pom tias qhov poob ntawm cov podocytes hauv cov zis cuam tshuam nrog qhov hnyav ntawm histology puas thiab qib ntawm glomerulosclerosis hauv lub raum biopsy, thiab cov neeg mob uas tsis muaj mob.tso zispodocyteexcretion muaj sai histological kev loj hlob.

Cov kev tshawb fawb ntawm podocyte-specific molecules hauv cov zis raws li biomarkers ntawm IgAN yog fragmented thiab tsis tiav. Cov theem ntawm cov zis podocalyxin cuam tshuam nrog qhov hnyav ntawm cov kab mob ntxiv capillary hauv cov neeg laus IgAN [102]. Cov theem ntawm cov zis podocin mRNA tau raug tshaj tawm los qhia txog qhov hnyav ntawm kev raug mob glomerular nyob rau hauv lub raum biopsy thiab muab cov ntaub ntawv prognostic ntxiv rau qib proteinuria [104]. Txij li thaum IgAN yog thawj hom kab mob glomerulonephritis thoob plaws ntiaj teb, xav tau kev tshawb fawb ntau ntxiv hauv thaj chaw no.

Ntxiv rau IgAN, lub luag haujlwm ntawmtso zispodocyteCov cim tau raug tshawb nrhiav hauv lwm cov mesangial glomerulopathies. Piv txwv li,tso zispodocyteKev poob yog nce ntxiv nyob rau hauv ob qho tib si hereditary thiab tau txais cov ntaub ntawv ntawm diffuse mesangial sclerosis [102]. Txawm li cas los xij, thaj chaw no tsis tau kawm zoo, tej zaum vim yog heterogeneity hauv nws cov kev faib tawm pathological.

3.5. Lupus nephritis

tso zispodocyteKev kho mob ntawm lupus nephritis tau kawm. Ib tsab ntawv tshaj tawm dhau los qhia tias qhov loj ntawmtso zispodocytesHauv cov neeg mob uas muaj mob lupus nephritis tau siv tau tab sis dedifferentiated, thiab qhov feem pua ​​​​ntawm apoptotic podocytes hauv cov zis tau qis dua li hauv kev tswj hwm kev noj qab haus huv [105]. Hauv txoj kev tshawb no, urinary podocalyxin, synaptopodin, podocin, nephrin, thiab WT-1 qib (raws li ntsuas los ntawm sab hnub poob blotting) tau nce ntau hauv cov kab mob lupus, tshwj xeeb tshaj yog nyob rau hauv cov mob lupus nephritis, thiab lawv cov qib sib cuam tshuam nrog cov proteinuria hnyav heev. thiab kev ua haujlwm histological [105]. Ib txoj kev tshawb fawb txuas ntxiv tau tshaj tawm tias cov zis mRNA qib ntawm nephrin, podocin, thiab synaptopodin tau nce siab dua hauv cov neeg mob uas muaj mob lupus nephritis dua li hauv quiescent lupus [106]. Tshwj xeeb, urinary nephrin mRNA qib sib cuam tshuam nrog cov proteinuria thiab cov kab mob hauv lub cev, tab sis tsis yog cov chav kawm histological ntawm lupus nephritis, thaum lub urinary podocin mRNA qib yog ib qho kev kwv yees ntawm lub raum ua haujlwm tom qab poob [107].

3.6. Anti-neutrophil cytoplasmic antibody (ANCA) - cuam tshuam vasculitis

Txawm hais tias podocytes tsis yog lub hom phiaj tseem ceeb ntawm lub raum raug mob hauv ANCA-koom nrog glomerulonephritis, intra-glomerular podocyte ceev yog tus yam ntxwv txo [108]. Zou et al [108] pom tias tus nqi ntawm podocyte detachment rau cov zis kwv yees ua rau lub raum tsis ua haujlwm tom qab hauv ANCA-koom nrog glomerulonephritis, thiab Minakawa et al [109] qhia tias tso zis podocin rau nephrin mRNA piv, ib tus neeg sawv cev ntawm podocytelonephritis. kev ntxhov siab, cuam tshuam nrog feem pua ​​​​ntawm crescent tsim [109]. Hauv kev tshawb fawb tom kawg, cov neeg mob uas muaj qib siabtso zispodocyte-derived mRNA tau muaj txiaj ntsig zoo rau lub raum, suav tias yog vim qhov zoo dua glomerular podocyte cia thiab muaj peev xwm rov qab los [109].

3.7. Lwm yam CKD

Qhov kev siv ntawmtso zispodocytecov cim tshwj xeebraumkab mobtau muab sau tseg rau hauv Table 3. Ntau tus lej ntawm cov cim qhia tshwj xeeb hauv cov zis kuj tau tshawb pom raws li cov cim tseem ceeb ntawm CKD(Chronicraumkab mob). Piv txwv li,tso zispodocyte-derived extracellular microvesicles, raws li quantified los ntawm flow cytometry, tau loj hlob nyob rau hauv cov neeg mob ntshav siab uas muaj lub raum tsis ua hauj lwm ntau dua li cov uas tsis muaj lub raum tsis zoo [110]. Cov zis synaptopodin qib, raws li kev txiav txim siab los ntawm Western blotting, cuam tshuam nrog lub raum ua haujlwm hauv ob qho tib si mob ntshav qab zib thiab tsis mob ntshav qab zib CKD.(Chronicraumkab mob), tsis hais txog qib ntawm albuminuria, qhia tias cov zis synaptopodin yog ib qho cim ntawm kev puas tsuaj rau podocyte [110]. Ntawm ib lub vaj huam sib luag ntawm podocyte-specific urinary mRNA lub hom phiaj, urinary hlwb-derived neurotrophic factor (BDNF) mRNA theem muaj qhov zoo tshaj plaws correlation nrog urinary raum raug mob molecule-1 (KIM-1), uas yog ib tug generic marker. lub raum puas [111] Rau cov hom phiaj miRNA, urinary exosomal miR-21 qib tau nce hauv cov tsiaj qauv ntawm kev raug mob podocyte nrog rau CKD(Chronicraumkab mob)cov neeg mob [112], tab sis lub hauv paus chiv keeb ntawm tes ntawm miR-21 tsis tau txiav txim siab hauv txoj kev tshawb no.

Txawm li cas los xij, nws tseem ceeb heev uas yuav tsum nco ntsoov tias tsis yog txhua tusraumkab mobmuaj kev raug mob podocyte. Kev nce hauvtso zispodocyteKev poob tau raug tshaj tawm nyob rau hauv ntau yam kab mob glomerular tab sis tsis yog nyob rau hauv autosomal dominant polycysticraumkab mob(ADPKD) [113]. Qhov tseem ceeb tshaj, kev koom tes ntawm podocyturia thiab proteinuria sib txawv ntawm cov kab mob glomerular sib txawv, qhia tiastso zispodocyteCov cim yuav tsum zoo dua suav tias yog kab mob tshwj xeeb [113].

4. Cov lus xaus

Kev raug mob Podocyte plays lub luag haujlwm tseem ceeb hauv cov kab mob thiab kev loj hlob ntawm ntau yamraumkab mob. Podocyte-derived cellular fragments thiab podocyte-specific molecular lub hom phiaj hauv cov zis muaj peev xwm tsim tau los ua biomarkers rau kev kuaj mob thiab kev saib xyuas ntawmraumkab mob. Cov txheej txheem ntawm kev txhim kho biomarker suav nrog kev txheeb xyuas cov cim tshwj xeeb, kev txiav txim siab ntawm cov txheej txheem ntawm kev ntsuas, thiab kev txiav txim siab ntawm cov ntsiab lus kho mob rau daim ntawv thov (Fig. 2). Nrog rau kev nce qib hauv peb txoj kev nkag siab ntawm podocyte biology thiab muaj cov thev naus laus zis tshiab,tso zispodocyteCov cim yuav tsum muaj kev nthuav dav ntawm daim ntawv thov, ob qho tib si vim yog kev txheeb xyuas cov hom phiaj tshiab thiab kev txhim kho ntawm cov txheej txheem tshiab rau lawv qhov kom muaj nuj nqis. Nyob rau hauv rov qab, validation ntawm urinary podocyte markers tej zaum yuav tso lub teeb rau peb to taub txog lub pathophysiology ntawmraumkab mob. Muaj ntau txoj hauv kev rau kev txheeb xyuas cov podocyte thiab ntau cov cim qhia tshwj xeeb hauv cov zis. Nyob rau hauv kaum xyoo tom ntej, kev tshawb fawb yuav tsum tau tsom mus rau standardizing, sib piv, thiab automizing laboratory txoj kev, nrog rau kev txhais lawv cov nqi ntxiv rau cov kev kuaj mob niaj hnub.

Fig. 2. Yam yuav tsum tau txiav txim siab rau kev txhim kho cov zis podocyte-txog biomarkers rauraumkab mob. (GCBM, glomerular capillary hauv qab daim nyias nyias; CKD,mob ntevraumkab mob; DKD, mob ntshav qab zibraumkab mob; FGS, focal glomerulosclerosis).

Tshaj tawm ntawm Kev Sib Tw Kev Txaus Siab

Cov kws sau ntawv tshaj tawm tias lawv tsis paub txog kev sib tw nyiaj txiag lossis kev sib raug zoo ntawm tus kheej uas tuaj yeem tshwm sim los cuam tshuam cov haujlwm tau tshaj tawm hauv daim ntawv no.

Kev lees paub

Txoj kev tshawb no tau txais kev txhawb nqa los ntawm Richard Yu Suav University of Hong Kong (CUHK) PD Research Fund, thiab CUHK tshawb fawb nyiaj 6905134 thiab 8601286. Cov neeg nrhiav nyiaj txiag tsis muaj lub luag haujlwm hauv kev tsim qauv, sau cov ntaub ntawv, thiab kev tshuaj xyuas, kev txiav txim siab luam tawm, lossis npaj cov ntawv sau. Cov kws sau ntawv tshaj tawm tsis muaj lwm yam kev tsis sib haum xeeb ntawm kev txaus siab. Cov txiaj ntsig tau nthuav tawm hauv daim ntawv no tsis tau luam tawm yav dhau los tag nrho lossis ib feem.

Txhim kho raum kab mob--Cistanche acteoside

Los ntawm: 'Urinary podocyte markers nyob rau hauvraumkab mob'los ntawmLingfeng Zeng, et al

---Clinica Chimica Acta 523 (2021) 315–324