Kev txheeb xyuas ntau hom kab mob raum mob ntev: urinary protein thiab peptide markers

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

Ntu Ⅰ: Cov Protein Urinary Protein thiab Peptide Markers nyob rau hauv Kab Mob Raum Ntev

Natalia Chebotareva, Anatoliy Vinogradov & et al.

1. Taw qhia

Raws li TheKab mob raum: Txhim Kho Ntiaj Teb Cov Txheej Txheem (KDIGO) cov txheej txheem,mob raum mob(CKD) txhais tau tias yog qhov txawv txav ntawm lub raum qauv lossis kev ua haujlwm tam sim no rau ntau tshaj 3 lub hlis, nrog rau kev noj qab haus huv [1,2]. CKD (mob raum mob)yog ib qho kev pheej hmoo txaus ntshai rau kev tuag, kab mob plawv, kab mob hauv lub raum kawg, thiab mob raum mob [3-7] thiab muaj kev kis thoob ntiaj teb ntawm 11-13 feem pua ​​[8]. CKD (mob raum mob) yog ib qho teeb meem tseem ceeb ntawm kev sib raug zoo vim muaj kev pheej hmoo siab ntawm kev xiam oob khab thaum ntxov los ntawm tus kab mob thiab xav tau kev kho tus nqi siab thaum lub raum tsis ua haujlwm, xws li hemodialysis, peritoneal dialysis, thiab hloov raum [9,10] . Peb feem ntau ua rau CKD (mob raum mob)yog ntshav qab zib mellitus, kub siab, thiab glomerulonephritis, tshwj xeeb tshaj yog nrog nephrotic syndrome [11].Kab mob raumtuaj yeem muaj cov tsos mob zoo sib xws thiab tej zaum yuav txawv ntawm qhov mob me thiab mob hnyav mus rau kev loj hlob sai nrog rau kev loj hlob sai ntawm cov kab mob raum. Txawm li cas los xij, qhov mob hnyav ntawm kev kho mob tshwm sim, txawm li cas los xij, tsis yog ib txwm cuam tshuam rau lub raum puas tsuaj, uas tuaj yeem txiav txim siab los ntawm lub raum biopsy [12]. Feem ntau ntawm cov neeg mob tau txais ib lub raum biopsy los txiav txim siab morphological daim ntawv ntawmmob raum. Hauv cov xwm txheej tsis sib xws, kev kuaj ntshav biopsy yog rov qab los ntsuas qhov ua tau zoo ntawm kev kho thiab kev kwv yees. Txawm li cas los xij, qhov kev ntsuam xyuas ntawm qhov regression ntawm nephropathic kev ua ub no tseem ceeb heev rau kev soj ntsuam kev kho mob, nrog rau kev kho kom zoo, kev ua kom zoo, thiab kev kwv yees.

Kab mob raum:mob raum mob (CKD)

Nyem rau cistanche phiv thiab Cistanche khoom

tso zisproteomictsom xamyog ib qho kev xaiv muaj kev nyab xeeb ntau dua piv rau biopsy thiab muaj peev xwm zoo rau kev tsim cov kev kuaj mob uas tsis muaj kev cuam tshuam. Kev tsom xam cov zis muaj ntau yam zoo piv rau cov ntshavproteomictsom xam[13]. Ua ntej, cov zis proteome tsis nyuaj heev thiab feem ntau muajcov proteinsthiabpeptidesntawm lub raum keeb kwm (txog li 70 feem pua). Ntawm qhov tsis sib xws, cov cim kev puas tsuaj rau lub raum tsuas yog ib feem me me ntawm cov ntshav plasma / serum proteome, uas ua rau lawv qhov kev soj ntsuam hauv qhov nyuaj kawg. Qhov thib ob, nws yog qhov yooj yim dua rau normalize qhov concentration ntawm aprotein ntaubiomarker nyob rau hauv cov zis tshaj nyob rau hauv cov ntshav - piv txwv li, raws li cov concentration ntawm creatinine [14]. Thib peb, kev sau cov zis yog yooj yim thiab tsis cuam tshuam. Thaum kawg, cov zis kuaj tau ruaj khov ntawm qhov kub ntawm -20 degree thiab haum rauproteomictsom xamtxawm tias tom qab xyoo ntawm kev khaws cia [15]. Cov txiaj ntsig tau hais los saum no ntawm cov zis ua rau nws yog ib qho tseem ceeb rau kev tshawb nrhiavprotein ntauCov cim rau ntau yam pathologies [16]. Cov pathologies muaj xws li raum thiab genitourinary pathologies thiab pathologies txuam nrog proteinuria, xws likab mob raum[17-19; zais zis, prostate, thiab qog nqaij hlav zes qe menyuam [20-23]; mob ntshav qab zib nephropathy [24]; thiab pre-eclampsia [25-27]. tso zisprotein ntauCov cim tseem tau piav qhia txog kab mob qog noj ntshav thiab lub ntsws [28,29], cholangiocarcinoma [30, kab mob plawv [31, kab mob autoimmune [32], thiab kis kab mob [33]. Txawm li cas los xij, cov zis proteome yuav tsum yog cov ntaub ntawv tshaj plaws rau lub raum pathologies thiab tuaj yeem nthuav tawm cov ntiv tes sib txawv.kab mob raum[34-39] (Table 1).

Txawm li cas los xij, txawm hais tias muaj ntau cov kev tshawb fawb, tseem tsis tau muaj kev ntseeg siab rau lub raum-kab mob tshwj xeeb biomarkers uas tuaj yeem raug tsim tawm hauv cov kev tshawb fawb sib txawv. Muaj ntau yam cuam tshuam rau proteome muaj xws li kev sau thiab kev tswj hwm (thaum sawv ntxov, txhua hnub, kev hloov pauv ntau hnub, thiab lwm yam), kev ua haujlwm ntawm lub cev, khoom noj khoom haus, cov yam ntxwv ntawm lub raum (tsis muaj lub raum, thiab lwm yam). , poj niam txiv neej, thiab hnub nyoog [40-43]. Tag nrho cov xwm txheej no yuav tsum raug coj mus rau hauv tus account thaum sib piv cov txiaj ntsig ntawm kev tshawb fawb sib txawv. Feem ntau, kev sib txuas cov cim ntawm cov nephropathies tshwj xeeb tau teev tseg hauv ntau qhov kev tshawb fawb tuaj yeem pab txhawb kev nce qib hauv kev tsim cov vaj huam sib luag tshwj xeeb rau kev siv tshuaj kho mob tom qab ntau theem yav tom ntej validation [44].

Table 1. Kev tshawb fawb txog zis proteome hauv ntau hom nephropathies

Mass spectrometry (MS)-raws li txoj hauv kev, uas muaj peev xwm ua kom muaj peev xwm ntau, yog cov cuab yeej tsis sib haum xeeb tshaj plaws thiab rhiab heev thiab twb tau muab ntau cov ntaub ntawv tam sim no paub txog cov zis.peptidethiabprotein ntaucov ntsiab lus nyob rau hauv sib txawv nephropathies, nrog rau tej zaum biomarker panels rau ntau yam kab mob [37-39]. Muaj ntau txoj hauv kev MS tau ua tiav (Table 1). Cov kev siv feem ntau suav nrog matrix-pab laser desorption / ionization lub sij hawm-ntawm-flight (MALDI-TOF), capillary electrophoresis (CE), thiab kua chromatography (LC) MS. Cov kev tshaj lij tshaj plaws nrog isobaric lossis tandem pawg cim npe rau cov txheeb ze thiab cov khoom muaj tseeb (iTRAQ thiab TMT) pab txhawb kev txheeb xyuas cov cim ntawm cov feem ntau tam sim nocov proteinsthiabpeptidesthaum lawv cov nyiaj sib txawv heev. Feem ntau, cov txheej txheem MS uas tsis tau teev tseg yog qhov tsim nyog tshaj plaws rau kev tshawb nrhiav thawj zaug ntawm biomarkers muaj peev xwm, thaum lub hom phiaj MS thiab immunoassays tuaj yeem siv rau kev siv tau ntxiv.

Qhov kev tshuaj xyuas no suav nrog cov ntaub ntawv los ntawm ntau cov kev tshawb fawb ntawm cov zis proteome hauv nephropathies txuam nrog CKD (mob raum mob), nrog rau kev tsom mus rau cov kev tshawb fawb tsis ntev los no los ntawm 2015 txog 2021. Cov ntaub ntawv hluav taws xob hauv MEDLINE, PubMed, thiab Cochrane tau tshawb fawb siv cov lus tseem ceeb xws li "proteomics""peptidomics","biomarkers","mob raum mob"," zis","membranous nephropathy""IgA nephropathy","focal segmental glomerulosclerosis""mob-hloov kab mob","diabetic nephropathy", thiab"lupus nephritis". Cov ntaub ntawv ntawm 1030 cov ntaub ntawv khaws tseg tau raug tshuaj xyuas, thiab cov ntaub ntawv uas tsis cuam tshuam lossis tsis ntseeg tau, cov ntawv tsis muaj nyob hauv cov ntawv nyeem, thiab cov ntawv tsis yog lus Askiv raug tshem tawm.

2. Kab mob raum (CKD)

Ntau qhov kev tshawb fawb txog urinary proteome tau xav txog CKD (mob raum mob)pawg pathologies tsis muaj subdivisions. Harald Mischak pawg yog tus thawj coj hauv MS cov kev tshawb fawb txog kev tso zis peptidome thiab proteome. Cov pab pawg no tau piav qhia txog 1580 haiv neeg tso zispeptides, qhia tias 73 feem pua ​​​​yog qhov tshwj xeeb rau cov zis thiab ua pov thawj tus nqi kho mob ntawm cov zis ib txwm muaj.peptideCov cim rau kev kuaj mob ntau yam kab mob, suav nrog cov uas cuam tshuam nrog rau lub raum puas[14,77,78].

Rossing K. et al. tsim thawj vaj huam sib luag muaj 65 tso ziscov proteins, suav nrog collagen fragments, serum albumin, o1-antitrypsin(A1AT), thiab uromodulin, uas txawv diabetic nephropathy nyob rau hauv 97 feem pua ​​​​ntawm cov neeg mob, qhia siab rhiab heev thiab tshwj xeeb ntawm 148 hom 2 DM thiab DN cov neeg mob [72]. Lub vaj huam sib luag tau ua tiav tiav los ntawm Alkhalaf A.et al. [79].

Nyob zoo DMet al. soj ntsuam cov zis kuaj los ntawm 476 tus neeg mob nrog CKD (mob raum mob)(feem ntau yog mob ntshav qab zib nephropathy) thiab 379 tswj thiab tsim ib qho kev faib tawm raws li 273 urinarypeptides(CKD (mob raum mob)273) nyob rau hauv daim ntawv ntawm ib tug composite CKD (mob raum mob)biomarker [45]. Lub vaj huam sib luag muaj cov khoom tawg ntawm collagen hom I thiab ⅢI -chains (181peptides), uas qhia txog qhov kev hloov pauv ntawm cov cellular matrix thiab txo cov kev ua haujlwm protease hauv qhov chaw. CKD (mob raum mob)Cov neeg mob kuj pom tau tias muaj kev tso zis ntau ntxiv ntawm plasmacov proteinsthiab lawv cov fragments (piv txwv li, A1AT, serum albumin, o-hemoglobin saw, thiab -fibrinogen saw), raum tshwj xeebcov proteins(uromodulin, gamma-chain Nat / K ntxiv rau -ATPase, thiab daim nyias nyias muaj feem xyuam nrog progesterone receptor tivthaiv 1), thiabcov proteinstso tawm los ntawm cov tubules, uas tuaj yeem cuam tshuam kev puas tsuaj rau lub glomerular filtration barrier, nce glomerulosclerosis, thiab interstitial fibrosis. Hauv kev tshawb nrhiav qhov muag tsis pom, CKD (mob raum mob) 273 tus txheej txheem ua kom nws muaj peev xwm sib txawv cov neeg mob nrog CKD (mob raum mob)ntawm ntau yam etiologies nrog 85.5 feem pua ​​​​rhiab heev thiab 100 feem pua ​​​​qhov tshwj xeeb thiab kwv yees qhov kev tuag ntawm hom 2 DM nrog microalbuminuria [45,80,81]. Cov txiaj ntsig no tau lees paub ntxiv los ntawm Schanstra .P.et al.[18] thiab Pontillo C.et al. [46 leej twg tau lees paub qhov kev faib tawm no tus nqi raws li tus kwv yees ntawm lub raum kev ua haujlwm tsis zoo thiab ua rau pom qhov txo qis hauv glomerular pom tus nqi ntawm<60 ml/min="" over="" 5="" years="" of="" monitoring.="" zürbig="" p="" et="" alshowed="" that="" the="" ckd273="" classifier="" could="" predict="" the="" development="" of="" diabetic="" nephropathy="" 1.5="" years="" before="" the="" onset="" of="" microalbuminuria.="" argiles="" a.et="" al.="" used="" the=""> (mob raum mob) 273 kev faib tawm ntawm 53 tus neeg mob nrog CKD (mob raum mob)thiab cov neeg mob sib txawv raws li lawv cov qib ntawm kev ua haujlwm tsis zoo ntawm lub raum thiab kev pheej hmoo ntawm theem kawg CKD (mob raum mob)los yog tuag [17].

Catanese L. et al. tsim cov FPP_29BH classifier, uas muaj 29 tshwj xeeb fibro-sis biomarkers rau cov neeg mob uas muaj ntau yam kev tiv thaiv kab mob thiab tsis muaj zogkab mob raum. Cov neeg mob lub raum fibrosis pom tias muaj kev nce ntxiv hauv cov zis proteases (cathepsin D, matrix metalloproteinase 2, collagenase 3, thiab matrix metalloproteinase-14), -2-HS-glycoprotein, lossis fetuin-A, thiab 19 sib txawv collagenpeptidefragments ntawm yim sib txawv collagen chains nrog sib txawv intensities ntawm cov neeg mob uas muaj siab thiab tsis tshua muaj degrees ntawm fibrosis [47].

Los ntawm CKD (mob raum mob)yog ib lub kaus rau ntau yam mob uas cuam tshuam rau ob lub raum, ntau ntawm cov cim tau hais tseg tsis yog kab mob tshwj xeeb. Kev tshawb fawb ntawm 1180 cov qauv tso zis los ntawm Siwy J.et al. tau qhia tias ntau cov cim tseem nyob ib yam ntawm cov nephropathies sib txawv thiab muaj kev cuam tshuam txog cov txheej txheem pathological [54]. Txawm li cas los xij, qhov kev tshawb fawb loj no tau txheeb xyuas ntau tus cim tshwj xeeb. Peb ntu ntawm pawg tau pom tias muaj ntau ntxiv hauv cov ntshav qab zib nephropathy, -2-microglobulin tau txo qis hauv cov kab mob hloov pauv tsawg, thiab S100-A9protein ntaufragment distinguished lupus nephritis [54]. Lwm yam tshwj xeebproteomicsthiab peptidomics hloov hauv ntau yam CKD (mob raum mob)hom, suav nrog cov kab mob hloov me me (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), mob ntshav qab zib nephropathies (DN), thiab lupus nephritis (LN), raug tshuaj xyuas hauv qab no.

3. Kev hloov pauv tsawg tsawg thiab Focal Segmental Glomerulosclerosis

Tsawg-hloov kab mob(MCD)thiab thawj focal glomerulosclerosis (FSGS) yog cov kab mob nrog thawj podocyte raug mob (primary podocytopathies), uas yog manifested li high proteinuria thiab nephrotic syndrome 82,83]. Txawm li cas los xij, kev tshawb fawb morphological ntawm lub raum biopsy nyob rau theem pib ntawm FSGS tuaj yeem nco segmental sclerosis hauv ib tus neeg glomeruli thiab tuaj yeem faib cov kab mob tsis zoo li MCD (Tsawg-hloov kab mobIb.) [84]. Thawj FSGS pathogenesis yog txuam nrog circulating permeability yam (xws li soluble urokinase-type plasminogen activator receptor (SuPAR), corticotrophin zoo li.protein ntau-1, thiab anti-CD40 antibody CD-80 qhia), uas ua rau kev loj hlob ntawm nephrotic syndrome [85-91]. Feem ntau, piv rau FSGS, MCD (Tsawg-hloov kab mob) muaj kev pom zoo ntau dua txog kev ua haujlwm ntawm lub raum tsis ua haujlwm; FSGS feem ntau yuav txhim kho txoj kev kho mob thiab ua rau lub raum tsis ua haujlwm sai thiab tseem yuav xav tau kev kho mob hnyav thiab tsis tu ncua [83,92,93]. Tsis tas li ntawd, qhov muaj qhov thib ob FSGS cuam tshuam rau kev kuaj mob thiab kho kab mob. Vim nws tsis muaj kev tiv thaiv kab mob, daim ntawv ntawm tus kab mob no tsis tas yuav siv tshuaj tiv thaiv kab mob [1.

Ntau qhov kev tshawb fawb tau tsom rau kev txheeb xyuasproteomicQhov sib txawv ntawm ob nephropathies no. Tshwj xeeb, nws tau pom tias calretinin thiab UBA52 qib siab dua hauv FSGS [4849], thaum 39S ribosomalprotein ntauL17 tau siab dua hauv MCD (Tsawg-hloov kab mob) [48](Table 2). Cov qib siab dua ntawm cathepsin B, cathepsin C, thiab annexin A3 tau pom nyob rau hauv cov xwm txheej ntawm qhov sib txawv ntawm FSGS (tus cwj pwm los ntawm glomerular collapse thiab ua rau lub raum tsis ua haujlwm sai) dua li hauv MCD (Tsawg-hloov kab mob), MN, thiab lwm yam FSGS variants [94]. Ob peb lub cim muaj peev xwm tshwj xeeb rau FSGS suav nrog nce qib ntawm cadherin-zoo li 26, RNase A tsev neeg 1, DIS3-zoo li exonuclease 1[50], matrix-remodelingprotein ntau8 [51], CD59, zoo li insulin-zoo li kev loj hlob zoo tshaj plaws-binding protein7, thiab roundabout homolog 4 [52], nrog rau kev txo qis hauv cov polymeric immunoglobulin receptor thiab Golgi-txuas nrog olfactory signaling regulator [54] lossis ua tiav tsis muaj dipeptidase. 1 (NPEP1)[52]. Kev nce qib CD14 tau pom tias yog tshwj xeeb rau MCD nkaus xwb (Tsawg-hloov kab mob) [50] thiab tsis tau txheeb xyuas lwm yam nephropathy (Table 2). Nyob rau tib lub sijhawm, kev nce hauv transferrin thiab histatin -3 tuaj yeem paub qhov txawv ntawm FSGS thiab MCD (Tsawg-hloov kab mob) [48] ​​los ntawm lwm yammob raum.

Ntawm cov cim qhia txog qhov muaj peev xwm, qhov tshaj tawm ntawm ribonuclease 2 thiab kev tsis txaus ntseeg ntawm haptoglobin tuaj yeem qhia qhov phem tshaj FSGS, thaum apolipoprotein A1 thiab matrix-remodelingprotein ntau8 (MXRA8) tau qhia txog kev hloov pauv tseem ceeb ntawm steroid-sensitive thiab steroid-resistant cov ntaub ntawv ntawm FSGS[51].

Feem ntau, muaj feem ntau ntawm cov lus hais saum toj nocov proteinsnyob rau hauv cov zis thiab nce nyob rau hauv lawv cov qib yuav muaj kev cuam tshuam loj heev cell tuag thiab tso tawm ntawm intracellular ntsiab lus thaum lub sij hawm lub podocytes 'kev sib cais los ntawm glomerular membrane. Cov txiaj ntsig no kuj tseem yuav qhia txog lub luag haujlwm tshwj xeeb rau kev tiv thaiv kab mob, mob, thiab apoptosis hauv kev txhim kho FSGS. Kev loj hlob ntawm tes, kev sib txawv, thiab kev tuag tuaj yeem koom nrog hauv MCD (Tsawg-hloov kab mob) kev loj hlob [95]. Dynamic cov kev tshawb fawb tau ua los ntawm kev siv focal segmental glomerulosclerosis nas qauv (adriamycin (ADR)-induced nephropathy) tau nthuav tawm ib qho kev nce ntxiv hauv afamin thiab ceruloplasmin, nrog rau kev txo qis hauv cadherin -2 thiab aggrecan core.protein ntauhauv FSGS, thiab qhia tias txo qis ntawm fetuin-B, -1-microglobulin, thiab -2-HS-glycoprotein tej zaum yuav yog cov cim cim rau kev tshawb pom ntxov ntawm FSGS [96]. Lwm qhov kev lag luam pheej hmoo suav nrog CD44, MXRA8, cathepsins, thiab apolipoprotein A1. CD44 qhia txog kev ua kom cov parietal epithelial hlwb, uas ua rau glomerulosclerosis. MXRA8 cathepsins koom nrog hauv kev sib txuam ntawm fibrosis thiab kab mob kev loj hlob. Apolipoprotein A1 qhia txog oxidative kev nyuaj siab, cuam tshuam nrog hyperlipidemia, thiab sawv cev rau ib qho ntawm cov kab mob hauv kev loj hlob ntawm FSGS.

Kev kuaj mob raum:tso zisproteomictsom xam

NYEEM NO PART Ⅱ