Cov Yam Tseem Ceeb Loj Loj: Muaj peev xwm Biomarkers Thiab Cov Hom Phiaj Kho Mob hauv Cov Kab Mob Raum Ⅱ

Fibroblast Growth Factors

Fibroblast loj hlob yam(FGFs) yog pleiotropic proteins koom nrog ntau yam kev lom neeg thiab kev ua haujlwm ntawm pathological los ntawmtswj kev sib txawv ntawm tes,kev loj hlob, kev tsiv teb tsaws chaw, thiabciaj sia. Nees nkaum-ob FGF ligands thiab tsib FGF receptors (FGFRs) suav nrog FGFR1-4 thiab FGFRL1 tau raug txheeb xyuas. FGF/FGFR plays lub luag haujlwm tseem ceeb hauvkev loj hlob ntawm lub raumthiab hauvpathogenesis ntawm lub raum kab mob[47]. Hauv xyoo tas los no, endocrine FGF21 thiab FGF23 muajattracted ntau xim nyob rau hauv lub teb ntawm cov kab mob raum. Kev nce siab ntawm FGF21 qib tau tshaj tawm hauv dyslipidemia, insulin tsis kam, metabolic syndrome, T2D, kab mob tsis zoo rau lub siab, atherosclerosis, thiab kab mob plawv [48], tag nrho cov ntawm lawv yog qhov tseem ceeb ntawm kev pheej hmoo rau CKD kev loj hlob. Qhov tseem ceeb, qhov nce qib ntawm cov ntshav FGF21 tau kuaj pom nyob rau hauv cov neeg mob uas muaj theem 2 CKD, thiab cov ntshav FGF21 concentration nce zuj zus nrog kev loj hlob ntawmCKDlos ntawm theem pib mus rau theem kawg [47, 48]. Ib txoj kev tshawb fawb tau xaus lus tias cov ntshav FGF21 qib tsis zoo cuam tshuam nrog rau lub raum ua haujlwm [49]. Nws tau raug tshaj tawm tias FGF21 ncaj qha suppresses lub raum lipid tsub zuj zuj; thiab tiv thaiv lub raum fibrosis, o, thiab oxidative kev nyuaj siab [48], qhia tias FGF21 yog ib tug muaj peev xwm biomarker los yog kho tus neeg sawv cev rau CKD. FGF21 analog, LY2405319 tau tsim thiab kuaj los ntawm theem 1 kev soj ntsuam kuaj mob kom txo tau lub cev hnyav thiab ceev cov tshuaj insulin thiab txhim kho dyslipidemia hauv cov neeg mob T2D thiab rog [50].

Nyem qhov no kom tau txais TOP-QUALITY CISTANCHE FOR KIDNEY DISEASE

FGF23 yog secreted los ntawm cov pob txha cov ntaub so ntswg thiab khi rau ib tug complex ntawm -Klotho thiab FGFR1c, FGFR3c, los yog FGFR4 thiab tswj systemic phosphate homeostasis thiab vitamin D metabolism. Kev noj zaub mov phosphate loading, hypercalcemia, parathyroid hormone, thiab 1, 25-dihydroxyvita min D txhawb nqa FGF23 ntau lawm los ntawm cov pob txha. Lub caij no, FGF23 induces urinary phosphate excretion thiab inhibits synthesis ntawm 1, 25-dihydroxy vitamin D nyob rau hauv lub raum, thiab txo cov parathyroid hormone biosynthesis nyob rau hauv lub caj pas parathyroid. Cov kev tshawb fawb tsis ntev los no ntawm FGF23 tau nthuav dav kev nkag siab ntawm pathophysiology ntawm cov ntxhia hauv cov kab mob metabolic hauv CKD. Hauv cov neeg mob thiab tsiaj txhu nrog CKD, plasma FGF23 qib tau nce ntxov ua ntej lwm yam kev hloov pauv hauv cov metabolism hauv cov ntxhia, qhia tias FGF23 ntau dhau yog qhov tseem ceeb rau kev tswj hwm cov phosphate hauv CKD thiab lub ntsiab ua rau tom qab 1,25-dihydroxy vitamin D tsis txaus thiab theem nrab hyperparathyroidism. Kev txo qis ntawm Klotho nyob rau hauv lub raum cov ntaub so ntswg pom nyob rau hauv thaum ntxov theem ntawm CKD tau raug suav hais tias yog ib qho tseem ceeb tshaj plaws nyob rau hauv lub Upstream yam uas tsav FGF23 tshaj vim hais tias tsis tshua muaj siab plasma FGF23 yog pom nyob rau hauv thawj Klotho deficiency. Txawm li cas los xij, qhov kev xav no tseem muaj kev tsis sib haum xeeb, thiab qhov cuam tshuam tsis zoo ntawm FGF23 cleavage yog lwm txoj hauv kev [51]. Tsis tas li ntawd, qhov nce siab ntawm FGF23 qib tuaj yeem siv los ua biomarker rau kev kuaj mob thiab / lossis kev kuaj mob ntawm CKD [47, 52, 53] thiab cuam tshuam nrog kev tuag ntau ntxiv, cov xwm txheej cerebrovascular, atrial fibrillation, sab laug ventricular hypertrophy, thiab lub plawv tsis ua haujlwm. hauv CKD [51]. Cov qib siab FGF23 muaj kev phom sij rau erythropoiesis, kab mob plawv, thiab lub cev tiv thaiv kab mob, uas tuaj yeem ua rau muaj qhov tsis zoo ntawm CKD. Lub raum FGF23 qhia kuj nce rau hauv cov kab mob hauv lub raum, uas tuaj yeem txhawb cov lus teb inflammatory thiab fibrosis hauv lub raum [54]. Cov tswv yim kho mob sib txawv ntawm lub hom phiaj ntawm FGF23 tau tsim muaj xws li FGF23 antibody. Txawm li cas los xij, thaiv FGF23 los ntawm cov tshuaj tiv thaiv kab mob ua rau hyperphosphatemia thiab vascular calcification uas yuav ua rau muaj kev pheej hmoo ntawm kev tuag ntawm cov neeg mob CKD [47]. Tsis tas li ntawd, ntau qhov kev sim tshuaj tau ua los ntsuas qhov cuam tshuam ntawm cov tswv yim tsom rau kev noj zaub mov phosphate, xws li phosphate binder, ntawm kev txo qis ntawm FGF23 hauv CKD [51]. Hauv AKI, FGF23 tau nce ntau ntxiv hauv kev ncig thiab tso zis ntawm cov neeg mob thiab cov qauv tsiaj uas raug ntxias los ntawm ntau qhov kev thuam [3, 47]. Yog li ntawd, FGF23 tuaj yeem ua tus cim qhia ntxov rau qhov xwm txheej AKI, thiab tus neeg sib tw prognostic marker rau cov txiaj ntsig tsis zoo hauv cov neeg mob uas tsim AKI [47]. Seb FGF23 plays lub luag haujlwm tseem ceeb hauv kev sib kho AKI tseem yuav tau tshawb nrhiav.

Hepatocyte Growth Factor

Hepatocyte growth factor (HGF) yog Ameslikas cais raws li mitogen uas tuaj yeemtxhawb kev loj hlob ntawm hepatocytes[3]. Cov kev tshawb fawb tom qab tau pom tias HGF tuaj yeem khi rau c-met receptor qhia hauv cov hlwb epithelial thiab ua rau ntau lub hlwb hauv autocrine lossis paracrine yam [55]. Lub luag haujlwm ntawm HGF-c-met axis yog ze rau kev loj hlob ntawm embryonic, angiogenesis, kho cov nqaij mos, thiab mob qog noj ntshav. Nyob rau hauv lub raum, HGF feem ntau yog secreted los ntawm epithelial hlwb, mesangial hlwb, endothelial hlwb, thiab macrophages, thiab c-met receptors nyob rau hauv fibroblast thiab TECs [3, 12]. Hauv cov neeg mob uas muaj AKI thiab xav tau kev kho lub raum hloov hauv cov chaw kho mob hnyav (ICUs), qhov txo qis ntawm urinary neutrophil gelatinase-associated lipocalin (NGAL) thiab urinary HGF hauv thawj 14 hnub yog cuam tshuam nrog kev nce ntxiv ntawm lub raum rov qab [ 56] ib. Cov kev tshawb fawb ua ntej tau pom lub luag haujlwm ntawm HGF renoprotective nyob rau hauv ntau hom tsiaj qauv ntawm AKI thiab CKD, exerting anti-inflammato ry thiab regenerative teebmeem thiab tiv thaiv tubular cell apoptosis, epithelial-to-mesenchymal hloov, thiab fibrosis [12]. Tsis tas li ntawd, kev kho mob ntawm lub raum tu bule c-met ua rau lub raum raug mob hauv AKI nas qauv, qhia txog lub luag haujlwm tiv thaiv ntawm tubule tshwj xeeb c-met signaling [3]. Yog li, HGF thiab c-met ua lub hom phiaj zoo rau kev kho mob raum. ANG-3777, tsim los ntawm Angion Biomedica Corporation, yog ib qho me me molecule nrog HGF zoo li kev ua haujlwm [57]. Nyob rau theem 2 txoj kev tshawb fawb hauv cov neeg mob hloov lub raum uas qhia txog kev ua haujlwm qeeb qeeb, muaj cov teeb liab ua haujlwm zoo rau kev txhim kho lub raum hauv cov kev kho mob nrog ANG-3777, nrog rau kev nyab xeeb zoo [58]. Yog li ntawd, ib theem 3 mus sib hais ntawm ANG-3777 nyob rau hauv lub raum hloov cov neeg tau txais nrog ncua graft muaj nuj nqi tau tsim [59]. Tsis tas li ntawd, kev tshawb fawb ntau theem 2 los ntsuas kev nyab xeeb thiab kev ua tau zoo ntawm ANG-3777 hauv kev tiv thaiv AKI tom qab cov txheej txheem phais mob plawv uas cuam tshuam nrog kev mob plawv tseem tab tom pib (Fig. 2) [60].

Vascular Endothelial Growth Factors

Cov tsev neeg vascular endothelial kev loj hlob (VEGF) suav nrog ntau tus tswv cuab: VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E (Viral VEGF), VEGF-F (Ntsab venom VEGF), placental growth factor ( PGF), thiab endocrine qog-derived vascular endothelial kev loj hlob yam (EG VEGF). VEGF-A yog ib tus tswvcuab kawm tau zoo hauv VEGF tsev neeg los ntawm kev khi VEGF receptor (VEGFR)-1 thiab VEG FR-2 thiab tswj cov tshuaj angiogenesis. Nyob rau hauv lub glomerulus, VEGF-A secreted los ntawm mature podocytes khi rau VEGFRs ntawm glomerular endothelial cell (GEnC) thiab ntxiv txhawb GEnC proliferation, tsiv teb tsaws, thiab ciaj sia taus. Nyob rau hauv tib neeg lub raum, VEGF-A kuj qhia nyob rau hauv lub raum tubules, thiab VEGFR{13}} thiab VEGFR{14}} yog qhia nyob rau hauv GEnC thiab peri-tubular endothelial hlwb [61]. Nws yog ib qho tseem ceeb uas ntau lub isoforms ntawm VEGF-A xws li 121 txog 206 amino acids tuaj yeem tsim los ntawm lwm qhov exon splicing, thiab VEGF-A165 yog qhov tseem ceeb tshaj plaws. Tom qab ntawd, ib tsev neeg tshiab ntawm VEGF-A isoforms tshwm sim los ntawm lwm qhov 3 'splice site nyob rau hauv lub davhlau ya nyob twg exon 8 yog hu ua VEGF-Axxxb [62]. Muaj cov pov thawj muaj zog qhia tias ob qho tib si VEGF-A kev qhia thiab kev sib txuas yog cov tswj hwm lub raum ua haujlwm [61, 62].

Ob leeg podocyte tshwj xeeb VEGF-A depletion thiab VEGF-A overexpression hauv nas tau pom tias ua rauCKD[63]. VEGF-A inhibitors thiab VEGFR-2 inhibitors feem ntau yog siv rau hauv kev kho mob antiangiogenic ntawm kev mob qog noj ntshav, tab sis cov neeg ua haujlwm no feem ntau ua rau muaj kev mob tshwm sim ua rau lub raum puas tsuaj [64]. Qhov txo qis hauv lub raum qhia ntawm VEGF-A tau pom tias muaj feem cuam tshuam nrog GFR ntawm cov neeg mob CKD [65, 66]. Meanwhile, nce circulating thiab tso zis ntau ntau VEGF-A nyob rau hauv cov neeg mob uas muaj crescentic glomerulonephritis (CrGN) thiab DKD [67, 68]. Ntawm qhov tod tes, cov neeg mob nyob rau theem pib ntawm DKD nrog rau lub raum ua haujlwm zoo ib txwm qhia txog qib siab dua ntawm VEGF-A165b isoform txheeb ze rau VEGF-A165. Txawm li cas los xij, thaum lub sijhawm tom qab ntawm DKD, thaum kwv yees GFR tau poob qis, qhov kev nthuav qhia ntau ntxiv ntawm VEGF-A165b tau ploj mus [69]. Podocyte-specific overexpression ntawm VEGF-A165b nyob rau hauv lub raum cawm endothelial dysfunction nyob rau hauv lub raum kab mob, tawm tswv yim kev hloov ntawm VEGF A splicing yog ib tug muaj peev xwm kho txoj kev [61]. Qhov tseeb, ntau yam kev loj hlob thiab kev loj hlob zoo receptors kuj muaj qhov sib txawv ntawm qhov sib txawv thiab tau cuam tshuam rau cov kab mob raum [62].

Lwm cov VEGFs kuj koom nrog cov kab mob raum. Cov ntshav siab dua VEGF-C qib tau raug txheeb xyuas raws li qhov muaj peev xwm tshiab biomarker ntawm ntim cov xwm txheej hauv cov neeg mob nrog CKD [70], thiab cov ntshav siab dua VEGF-B thiab VEGF-D muaj feem cuam tshuam nrog lub raum tsis ua haujlwm hauv cov neeg mob DKD [71, 72] . VEGF-C thiab VEGF-D kuj koom nrog hauv lymphangiogenesis hauv lub raum fibrosis, thiab kev thaiv ntawm VEGF-C thiab VEGF-D signaling txo qhov cuam tshuam ntawm lymphangiogenesis [73]. Cov kev tshawb fawb no muab cov kev kho tshiab tshiab rau cov kab mob raum los ntawm kev tsom VEGF-B, VEGF-C, thiab VEGF-D. Piv txwv li, PGF yog ib qho ligand ntawm VEGFR-1, uas feem ntau siv los ua biomarker ntawm cov xwm txheej hauv plawv. Plasma PGF, GDF15, thiab FGF23 muaj feem cuam tshuam nrog kev kwv yees GFR poob ib xyoos ib zaug hauv kev sib piv los ntawm Uppsala Longitudinal Study of Adult Men (UL SAM), thiab cov kev loj hlob no tuaj yeem siv los kwv yees CKD tshwm sim [74]. Tsis ntev los no, PGF tau txheeb xyuas tias yog ib qho ntawm cov kev ua tau zoo tshaj plaws ntawm cov ntshav plasma biomarkers rau cov kab mob hauv lub raum kev loj hlob hauv kev tshawb fawb yav tom ntej ntawm 549 tus neeg uas muaj kab mob qog nqaij hlav hauv lub raum los ntawm kev siv cov tshuaj proteomics [75]. Lwm txoj kev tshawb fawb hauv 1,444 cov neeg laus uas tau txais kev phais mob plawv qhia tau hais tias ntau dua tom qab kev phais PGF yog nws tus kheej cuam tshuam nrog qis qis ntawm AKI, ntev AKI ntev, thiab kev tuag [76].

IGF System

Qhov kev loj hlob zoo li insulin (IGF) muaj xws li IGF-1 thiab IGF-2, hom I thiab hom II receptors (IGF-RI thiab IGF-RII), kev sib raug zoo IGF-binding proteins (IGFBPs). ), IGFBP-related proteins (IGBP-rPs), thiab IGFBP proteases. IGF-1 kho kom haum ntau yam kev loj hlob hormone ua. IGF system yog qhov tseem ceeb rau kev saib xyuas ntawm lub raum ua haujlwm ib txwm muaj, thiab kev ua haujlwm tsis zoo ntawm IGFs tau cuam tshuam rau ntau yam kab mob raum [77, 78]. Txawm li cas los xij, kev ua haujlwm ntawm IGF hauv cov kab mob hauv lub raum tseem muaj teeb meem. IGF kev ua haujlwm tau nce ntxiv hauv DKD thaum ntxov, qhov txo qis IGF ua rau muaj feem cuam tshuam rau CKD, qhia tias IGF system yuav tsum tau ua kom zoo sib npaug rau cov txiaj ntsig zoo rau lub raum [78]. Hauv CKD, cov ntaub ntawv pov thawj tau los ntawm cov qauv nas thiab tib neeg tau pom tias kev loj hlob hormone / IGF-1 / IGFB Ps axis koom nrog cov kab mob ntawm DKD, thiab IGF-1 plays lub luag haujlwm tseem ceeb hauv kev loj hlob thaum ntxov ntawm DKD [79, 80]. Hauv AKI, qhov txo cov ntshav IGF-1 qib muaj feem cuam tshuam nrog kev tuag ntau ntxiv thiab cov khoom noj khoom haus ntawm AKI cov neeg mob. Yog li ntawd, ntshav IGF-1 yog tus neeg sib tw tsim nyog raws li tus neeg sawv cev ntxov thiab muaj txiaj ntsig zoo rau AKI kev tuag hauv ICU [3]. Txawm hais tias IGF-1 tau pom tias muaj peev xwm kho tau hauv nas qauv ntawm AKI, qhov no tsis yog qhov tshwm sim hauv tib neeg AKI [3]. Nyob rau hauv xyoo tas los no, lub luag hauj lwm ntawm IGFBPs nyob rau hauv cov kab mob hauv lub raum tau them nyiaj ntau heev [81]. Ntawm lawv, IGFBP-7 tau qhia ntau heev hauvcev tubulesthiab feem ntau yog siv los ua qhov kev kwv yees thaum ntxov thiab prognostic marker rau AKI [81]. Cov zis com pound ntawm cov ntaub so ntswg inhibitor ntawm metalloproteinase-2 (TIMP- 2) thiab IGFBP-7 tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA) ua thawj biomarker rau kev soj ntsuam kev pheej hmoo ntawm AKI hauv ICU cov neeg mob hauv 2014 [81].

IGFBP-rP2, tseem hu ua cov ntaub so ntswg loj hlob (CTGF) lossis CCN2, tau nthuav dav hauv lub raum. CTGF tau kawm zoo vim nws yog tus neeg nruab nrab ncaj qha ntawm TGF- -induced fibrosis. Tam sim no, tsis muaj CTGF receptor tshwj xeeb tau raug txheeb xyuas. CTGF tuaj yeem ua rau nws cov teebmeem los ntawm kev khi ntau yam molecules, suav nrog kev loj hlob, matrix proteins xws li fibronectin thiab proteoglycans, thiab cell deg molecules xws li integrins, thiab qee cov receptors [7]. Nyob rau hauv lub raum, CTGF yog upregulated nyob rau hauv cov neeg mob nrog DKD, ntev allograft nephropathy, hypertensive nephrosclerosis, thiab CrGN [7]. Cov ntshav plasma thiab urinary CTGF qib tau nce siab hauv ntau yam CKD thiab ua raws li tus kws tshaj lij ywj pheej rau cov kab mob raum kawg [82]. Txawm hais tias FG-3019, ib qho tshuaj tiv thaiv CTGF tau txais txiaj ntsig zoo thiab ua rau txo qis ntawm microalbuminuria hauv ob theem 1 kev sim hauv DKD (Fig. 2); cov kev sim tshuaj hauv qab no hauv cov ncauj lus nrog FSGS thiab DKD raug tso tseg ua ntej [5].

Platelet-Drived Growth Factors

Platelet-derived growth factor (PDGF) yog qhov tseem ceeb hauv kev loj hlob ntawm cov kab mob hauv lub raum, tshwj xeeb tshaj yog cov uas muaj cov kab mob mesangial cell proliferation thiab interstitial fibrosis [4]. Tam sim no, ntawm plaub PDGF isoforms thiab ob PDGF receptor (PDGFR) subunits, tsib txawv PDGF dimers (PDGF-AA, PDGF-BB, PDGF-CC, PDGF-DD, thiab PDGF-AB) thiab peb PDGFR di mers (PDGFR- , PDGFR- , thiab PDGFR- ) raug tsim, feem. Hauv lub raum, PDGF yog tsim los ntawm ntau hom cell, suav nrog podocytes thiab TECs. PDGFs khi rau cov dimerized PDGFRs qhia ntawm mesenchymal hlwb nyob rau hauv lub raum thiab txhawb kev loj hlob thiab / los yog recruitment ntawm fibroblasts, mesangial hlwb, pericytes, thiab cov nqaij mos hlwb [4, 7]. Kev nthuav qhia ntau ntxiv ntawm cov ntsiab lus ntawm PDGF system tau pom nyob rau hauv lub raum los ntawm ntau yam kab mob raum, xws li mesangial proliferative glomerupathies, IgA nephropathy, CrGN, lupus nephritis, membranous nephropathy, thiab transplant glomerulopathy [4, 7, 83]. Lub PDGF-D circulating yog nce siab nyob rau hauv cov neeg mob uas muaj IgA nephropathy, thiab tso zis ntawm PDGF-A thiab PDGF-AB / PDGF-B kuj nce ntxiv rau cov neeg mob uas tsis muaj ntshav qab zib hom 1 [7].

Ntau qhov kev tshawb fawb hauv tsev kho mob tau pom tias qhov kev tawm tsam ntawm PDGF / PDGFR signaling tuaj yeem kho cov kab mob raum ntawm ntau yam etiologies. Hauv anti-Thy1 glomerular phritis nas qauv, kev kho mob nrog PDGFR / Fc chimeric molecule, oligonucleotide aptamer antagonist tiv thaiv PDGF-B, los yog PDGF-D-neutralizing antibody tuaj yeem txo cov mesangial proliferation thiab tiv thaiv kev loj hlob ntawm lub raum fibrosis [4] , 84] ib. PDGF-D deficiency ua rau txo qis hauv lub raum interstitial fibrosis hauv UUO thiab unilateral IRI qauv [4]. Ob qho tshuaj tiv thaiv PDGF-C IgG thiab PDGF-C tsis muaj peev xwm txo tau lub raum fibrosis hauv UUO qauv [7]. Tsis tas li ntawd, PDGFR kinase inhibitors, xws li imatinib thiab AG1295, txo lub raum fibrosis hauv cov qauv ntawm autoimmune nephritis, DKD, kub siab, thiab mob ntev allograft nephropathy [4]. PDGFR- tsis muaj peev xwm txhim kho glomerular thiab interstitial morphology hauv kev sim DKD [85]. Cov kev tshawb fawb no qhia tias PDGF system tuaj yeem sawv cev rau cov hom phiaj kho mob raum kab mob. Txawm li cas los xij, lub tswv yim no tseem tsis muaj kev siv cov kev tshawb fawb soj ntsuam.

Progranulin

Raws li kev loj hlob ntawm autocrine, progranulin (PGRN) muaj ntau yam kev ua haujlwm ntawm lub cev thiab muaj kev koom tes hauv cov kab mob ntawm ntau hom kab mob xws li kab mob autoimmune, atherosclerosis, thiab mob qog noj ntshav. PGRN tseem yog ib qho tseem ceeb los tiv thaiv kab mob molecule los ntawm lub hom phiaj ntawm proinflammatory signaling ntawm TNF. Peb cov kev tshawb fawb pom tias qib ntawm PGRN tau txo qis hauv lub raum hauv tus qauv nas ntawm lub raum IRI [86]. PGRN tsis muaj peev xwm hauv nas ua rau lub raum raug mob hnyav dua li qhov ua pov thawj los ntawm cov ntshav creatinine ntau dua, kev raug mob morphological ntau dua, thiab cov lus teb inflammatory [86]. Qhov tseem ceeb, tib neeg PGRN muaj peev xwm kho tau AKI [86]. Cov ntaub ntawv pov thawj tau pom tias nucleotide oligomerization domain (NOD)-zoo li receptors (NLRs) muaj kev koom tes hauv cov kab mob hauv lub raum [87]. Peb cov kev tshawb fawb ntxiv qhia tias PGRN, tsawg kawg yog ib feem, tsis zoo tswj cov lus teb inflammatory mediated los ntawm NOD2, ib tug tswv cuab ntawm NLRs [86]. Hauv cov kev tshawb fawb nram qab no, peb pom tias PGRN qhia hauv lub raum txo qis hauv cov nas mob ntshav qab zib thiab cov neeg mob biopsy-proven DKD [88]. PGRN tsis muaj peev xwm ua rau muaj kev raug mob podocyte ntau ntxiv, thaum tib neeg kev tswj hwm PGRN ua haujlwm tau zoo ua kom lub raum raug mob hauv cov nas mob ntshav qab zib [88]. Mechanistically, PGRN tuav mitochondrial homeostasis ntawm Sirt1-PGC-1 / FoxO1 signaling-mediated mitochondrial biogenesis thiab mitophagy thiab induces autophagy ntawm txoj kev CaMKK-AMPK, yog li tiv thaiv podocytes nyob rau hauv cov mob ntshav qab zib [88, Qhov txo qis rau lub raum PGRN kuj tau lees paub hauv CKD nas [90]. Interestingly, lub PGRN circulating yog nce nyob rau hauv tib neeg thiab tsiaj qauv ntawm AKI thiab CKD, qhia tau hais tias muaj zog circulating PGRN tej zaum yuav ib tug compensatory mechanism los txo lub raum tsis ua hauj lwm [90].

Myeloid-Derived Growth Factor

Myeloid-derived growth factor (MYDGF), yog Ameslikas pom tias yog paracrine protein secreted los ntawm cov pob txha pob txha-derived monocytes thiab macrophages [91]. Cov kev tshawb fawb tau pom tias MYDGF ua lub luag haujlwm tiv thaiv kab mob plawv. MYDGF kho lub plawv tom qab myocardial infarction [91, 92], txhawb nqa cardiomyocyte proliferation thiab txhim kho lub plawv regeneration nyob rau hauv nas tom qab mob plawv [93], inhibits endothelial puas thiab atherosclerosis nyob rau hauv apolipoprotein E knock-out nas [94], thiab tiv thaiv lub siab overload - mob plawv tsis ua hauj lwm [95]. Cov kev tshawb fawb tsis ntev los no tau pom tias MYDGF tseem koom nrog hauv cov kab mob hauv lub raum. Cov qib plasma ntawm MYDGF raug txo qis hauv cov nas mob ntshav qab zib thiab cov neeg mob [96]. MYDGF tsis tsuas yog txhim kho cov piam thaj / lipid metabolism hauv cov nas mob ntshav qab zib tab sis kuj txo qis kev raug mob podocyte DKD [96, 97]. Los ntawm tiam ntawm cov pob txha chimeric nas, lub luag haujlwm ntawm cov pob txha pob txha-los ntawm MYDGF hauv kev tswj cov piam thaj metabolism thiab lub raum ua haujlwm nyob rau hauv cov mob ntshav qab zib tau hais [97]. Tsis ntev los no, peb txoj kev tshawb fawb pom tias MYDGF kuj tau nthuav tawm hauv lub raum parenchymal hlwb thiab txo qis hauv podocytes los ntawm nas nrog FSGS thiab DKD [98]. Cov theem ntawm MYDGF hauv glomeruli tsis zoo cuam tshuam nrog cov zis albumin creatinine piv rau cov nas uas muaj kab mob glomerular [98]. Functionally, MYDGF tiv thaiv podocytes tiv thaiv mitotic kev puas tsuaj los ntawm kev txo cov tsub zuj zuj ntawm podocytes hauv S theem [98]. Qhov tseem ceeb tshaj, qhov txo qis ntawm MYDGF pom nyob rau hauv glomeruli los ntawm cov neeg mob uas muaj kab mob glomerular, thiab qib MYDGF cuam tshuam nrog GFR, ntshav creatinine, thiab podocyte poob, qhia tias MYDGF tuaj yeem yog lub hom phiaj kho mob zoo rau cov kab mob glomerular [98] .

Cov lus xaus

Tau ntau xyoo lawm, tus nqi ntawm kev loj hlob yam tseem ceeb raws li biomarkers thiab kho lub hom phiaj ntawm cov kab mob raum tau nyiam ntau yam. Ntau yam kev loj hlob tau pom tias lawv muaj peev xwm ua biomarkers rau kev kuaj mob raum kab mob (Table 1). Txawm li cas los xij, kev tshawb nrhiav tom qab nrog cov pab pawg loj thiab kev soj ntsuam ntev ntev yuav tsum tau ua kom raug ntau dua los txhais cov ntawv thov tus nqi ntawm qee qhov kev loj hlob ntawm qee theem ntawm qee yam kab mob raum. Ntawm qhov tod tes, kev ntsuam xyuas ntxiv ntawm kev sib xyaw ua ke ntawm biomarkers uas muaj qhov tsim nyog loj hlob yuav ua rau muaj kev kuaj pom tseeb ntawm cov kab mob raum. Nyob rau hauv nam ntawm kev kho lub hom phiaj rau cov kab mob raum (Table 2), txoj kev mus kom ze lub hom phiaj kev loj hlob yam tseem tsis tau txhais mus rau hauv ib tug zoo thiab muaj kev nyab xeeb txoj kev kho mob rau tib neeg, uas tej zaum yuav yog vim lub heterogeneity ntawm lub raum kab mob thiab lub pluripotency ntawm loj hlob yam. Nyob rau hauv lub neej yav tom ntej, cov kev kho mob ntawm lub raum kab mob yuav tsum tau ib tug neeg, uas yuav tsum tau mus rau lub deployment ntawm txawv ua ke ntawm cov neeg sawv cev rau txawv scenarios. Yog li ntawd, ntau qhov kev sim yuav tsum tau ua kom zoo dua cov tshuaj kho kom ua tiav cov txiaj ntsig tshwj xeeb, ruaj khov, thiab muaj txiaj ntsig zoo thiab zam lawv cov kev mob tshwm sim. Nyob rau tib lub sijhawm, kev kho cell-based thiab nucleic acid therapeutics yog txoj hauv kev zoo nkauj los pab txhawb kev kho mob txhais lus ntawm kev loj hlob ntawm cov kab mob raum, uas tuaj yeem muab cov tswv yim tshiab rau kev kho mob raum kab mob.

Cov ntaub ntawv

1 Guzeloglu-Kayisli O, Kayisli UA, Taylor HS. Lub luag haujlwm ntawm kev loj hlob thiab cytokines thaum cog: endocrine thiab paracrine cuam tshuam.Semin Reprod Med. Lub Ib Hlis 2009; 27(1):62–79 : kuv.

2 Silva AC, Lobo JMS. Cytokines thiab kev loj hlob yam.Adv Biochem Eng Biotechnol. 2020; 171:87–113. 

3 Gao L, Zhong X, Jin J, Li J, Meng XM. Poten tial tsom txoj kev kho thiab kev kuaj mob raws li kev pom tshiab rau hauv kev loj hlob, receptors, thiab downstream effectors nyob rau hauv mob raum raug mob thiab mob raum raug mob- mob raum kab mob.Teeb liab Transduct Target Ther. 2020 Peb 14; 5(1): 9.

4 Ruiz-Ortega M, Rayego-Mateos S, Lamas S, Ortiz A, Rodrigues-Diez RR. Lub hom phiaj ntawm kev loj hlob ntawm cov kab mob raum ntev.Nat Rev Nephrol. Peb Hlis 2020; 16(5): 269–88.

5 Allinovi M, De Chiara L, Angelotti ML, Becherucci F, Romagnani P. Anti-fibrotic kev kho mob: kev tshuaj xyuas cov pov thawj kho mob.Ma trix Biol. 2018 Aug; 68–69: 333–54.

6 Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-: tus tswv regulator ntawm fibrosis.Nat Rev Nephrol. Peb Hlis 2016; 12(6:325–38. 7 Kok HM, Falke LL, Goldschmeding R, Nguyen TQ. Targeting CTGF, EGF thiab PDGF txoj hauv kev los tiv thaiv kev mob raum.Nat Rev Nephrol. 2014 Dec; 10(12): 700–11. 8 Nguyen TQ, Goldschmeding R. Pob txha morphogenetic protein

7 thiab cov ntaub so ntswg loj hlob tuaj: lub hom phiaj tshiab rau kev kho mob raum fibrosis?Pharm Res. 2008 Nov; 25(10): 2416–26. 9 Nakamura J, Yanagita M. Bmp modulators nyob rau hauv mob raum.Discov Med. 2012 Jan; 13(68): 57–63. 10 Li RX, Yiu WH, Tang SCW. Lub luag haujlwm ntawm pob txha morphogenetic protein-7 hauv lub raum fibrosis.Pem hauv ntej Physiol. 2015;6:114.

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