Tsis yog-Coding RNAs nyob rau hauv keeb kwm ntawm lub raum Disorders Part 2

4.1.2. miR-21

miR-21 raws li evolutionarily conserved oncogenic miRNA yog qhia nyob rau hauv ntau yam kabmob, xws li lub plawv, ntsws, thiab raum [62]. miR-21 tau qhib rau hauv cov khoom thiab hematological malignancies, uas txhawb cov qog nqaij hlav los ntawm kev tswj cov qog nqaij hlav qog noj ntshav thiab apoptosis [63]. miR-21 kuj tau tshaj tawm tias inhibit apoptosis, thiab txhawb kev mob thiab fibrosis hauv ob lub raum [29]. Cov kev tshawb fawb tau qhia qhov zoo sib xws ntawm qhov tsis zoo ntawm kev taw qhia txoj hauv kev thiab pathological derangements ntawm cov qog thiab PKD [64]. miR-21 kuj yog upregulated nyob rau hauv lub raum los ntawm Pkd1 conditional knockout nas (Pkd1flflox/flox: Pkhd1-Cre nas), Pkd2 conditional knockout nas (Pkd2flox/flox: Pkhd1-Cre nas) , thiab HNF1B cov nas uas tsis muaj zog (Hnf-1 fllox/flox: Pkhd1-Cre nas), thiab hauv tib neeg ADPKD ob lub raum [36]. miR{18}} tuaj yeem qhib tau los ntawm cAMP/CREB txoj hauv kev, tus tsav tsheb paub zoo ntawm kev loj hlob cyst, qhov feem ntau tswj hwm los ntawm TGF- /SMAD txoj hauv kev mob qog noj ntshav thiab fibrosis [36,65,66]. Kev tshem tawm ntawm miR-21 txo qis cyst kev loj hlob hauv ADPKD nas qauv los ntawm inducing cyst epithelial cell apoptosis [36]. Peb txoj kev tshawb fawb yav dhau los tau tshaj tawm tias Smac-mimetic txo qis kev loj hlob ntawm cov cyst hauv Pkd1 cov kab mob hauv cov nas nas (Pkd1flflox/flox: Pkhd1-Cre nas) los ntawm inducing cyst-lining epithelial cell apoptosis nkaus xwb, uas muab thawj cov pov thawj uas induction ntawm cystic. epithelial cell apoptosis yog ib txoj hauv kev kho mob hauv PKD [67]. Ob peb inhibitors ntawm apoptosis (IAPs) qhia hauv lub raum, suav nrog Jag1, Pten, Spry, thiab Cdc25a, tau lees paub tias yog lub hom phiaj ntawm miR-21 [68]. Tsis tas li ntawd, cov qog nqaij hlav qog nqaij hlav, programmed cell death 4 (Pdcd4), kuj tau txheeb xyuas tias yog lub hom phiaj tshiab ntawm miR-21 hauv PKD [36]. Kev tshem tawm ntawm Pdcd4 tsim cov kab mob raum tsis tu ncua hauv Pdcd4−/− nas [69]. Yog li, qhov dysregulated qhia ntawm miR-21 txhawb nqa cyst kev loj hlob ntawm cAMP/CREB-miR-21-PDCD4 signaling axis thiab tau dhau los ua lub hom phiaj tshuaj tshiab hauv PKD. Cov tshuaj tiv thaiv-miR-21 tshuaj, RG-012, tau raug sim nyob rau hauv Phase 2 kev sim tshuaj rau kev kho mob Alport syndrome, raws li tau tham nyob rau hauv kom meej nyob rau hauv nqe lus hauv qab no, uas yuav tsum coj nws daim ntawv thov nyob rau hauv ADPKD kev kho mob yav tom ntej.

Raws li kev tshawb fawb cuam tshuam,cistancheyog ib txwm suav tshuaj ntsuab uas tau siv rau ntau pua xyoo los kho ntau yam kab mob. Nws tau raug pov thawj scientific kom muaj cov tshuaj tiv thaiv kab mob, tiv thaiv kev laus, thiab antioxidant zog. Cov kev tshawb fawb tau pom tias cistanche muaj txiaj ntsig zoo rau cov neeg mob uas raug mobkab mob raum.Cov khoom xyaw nquag ntawm cistanche paub tias txo qhov mob,txhim kho lub raum ua haujlwmthiab restore lub raum puas hlwb. Yog li, integrating cistanche nyob rau hauv ibkab mob raumKev npaj kho mob tuaj yeem muab txiaj ntsig zoo rau cov neeg mob hauv kev tswj hwm lawv tus mob.

Nyem rau Cistanche Tubulosa Extract

Nug ntau ntxiv: david.deng@wecistanche.com WhatApp:86 13632399501

Cistanchepab txo qis proteinuria, txo qis BUN thiab creatinine qib, thiab txo qhov kev pheej hmoo ntawm lub raum puas tsuaj ntxiv. Tsis tas li ntawd, cistanche kuj pab txo cov roj cholesterol thiab triglyceride qib uas tuaj yeem ua rau muaj kev phom sij rau cov neeg mobkab mob raum.

Cistanche's antioxidantthiab anti-aging zog pab rautiv thaiv lub raumlos ntawm oxidation thiab kev puas tsuaj los ntawm dawb radicals. Qhov no txhim kho lub raum noj qab haus huv thiab txo cov kev pheej hmoo ntawm kev tsim teeb meem.Cistanchekuj pab txhawb lub cev tiv thaiv kab mob, uas yog qhov tseem ceeb hauv kev tawm tsam cov kab mob raum thiab txhawb nqalub raum noj qab haus huv.

Los ntawm kev sib txuas cov tshuaj suav tshuaj ntsuab thiab cov tshuaj niaj hnub sab hnub poob, cov neeg txom nyem los ntawmkab mob raumtuaj yeem muaj ntau txoj hauv kev los kho tus mob thiab txhim kho lawv lub neej zoo.Cistancheyuav tsum tau siv los ua ib feem ntawm txoj kev npaj kho mob tab sis tsis yog siv los ua lwm txoj hauv kev kho mob.

4.1.3. miR-199a-5p

Nws tau raug tshaj tawm tias 30 miRNAs tau tswj hwm qhov sib txawv hauv lub raum ntawm Han: SPRD-cy nas los ntawm microarray-based mus kom ze [70]. Lwm qhov kev tshawb fawb ntxiv tau txheeb xyuas yim miRNAs (miR-199a-5p, -214, -146b, -21, -34a, {{ 10}}, -31, thiab -503) uas yog upregulated nyob rau hauv no PKD nas qauv [71]. miR-199a-5p tswj cov qog nqaij hlav qog noj ntshav, fibrosis, mob plawv hypertrophy, thiab angiogenesis, thiab tau tswj hwm hauv ADPKD cov ntaub so ntswg [37]. miR-199a{18}}p tau txwv tsis pub cov kev qhia ntawm CDKN1C/p57, uas yog lub zog nruj-binding inhibitor ntawm ob peb G1 cyclin / Cdk complexes thiab tus tswj tsis zoo ntawm cell proliferation [72]. Inhibition ntawm miR-199a-5p txo cov cell proliferation thiab nce apoptosis ntawm cyst epithelial hlwb los ntawm kev tsom CDKN1C/p57 [37].

MiRNAs uas tuaj yeem tsom qhov sib txawv ntawm mRNAs tau kwv yees los ntawm kev siv cov kev suav nrog, thiab cuaj miRNAs, suav nrog miRs-10a, -30a-5p, -96, {{4 }}p,-182, -200a, -204, -429, thiab -488, yog dysregulated nyob rau hauv lub raum los ntawm embryonic PKD1−/− nas [73 ]. Qhov kev qhia ntawm miR-200 yog downregulated nyob rau hauv Dicer conditional knockout nas uas muaj ib tug deletion ntawm Dicer nyob rau hauv cov laus lub raum tubules thiab tsim tubular thiab glomerular cysts [74]. MiR-200 txwv tsis pub cov kev qhia ntawm PKD1 nyob rau hauv ib qho posttranscriptional yam nyob rau hauv lub raum epithelial hlwb los ntawm kev khi nrog lub 30 -UTR ntawm PKD1 mRNA. Inhibition ntawm miR- 200 nyob rau hauv lub raum epithelial hlwb nce qhov kev qhia ntawm PKD1. Nws tau raug tshaj tawm tias Pkd1 transgenic nas reproducibly tsim tubular thiab glomerular cysts [38]. Yog li, kev txhim kho cyst hauv Dicer knockout nas yuav tshwm sim los ntawm kev hloov pauv ntawm PKD1 noob ntawm miR-200.

4.1.5. miR-25-3p

Autophagic influx yog inhibited nyob rau hauv Pkd1 knockout nas (Pkd1−/−), Han: SPRD Cy/Cy nas, thiab congenital polycystic raum (CPC) nas, thiab induction ntawm autophagy tau pom los suppress cyst kev loj hlob [75]. miR-25-3p yog qhia tsis meej nyob rau hauv cov qog nqaij hlav, uas tswj cov qog nqaij hlav qog nqaij hlav thiab autophagy [39]. miR-25-3p kuj raug tswj hwm nyob rau hauv lub raum cystic ntawm Pkd1flflox/-: Ksp-Cre nas. Inhibition ntawm miR-25-3p hauv tus qauv Pkd1 nas no nce autophagy tab sis txo qis lub raum cell proliferation [39]. miR-25-3p suppressed lub autophagy ntawm PKD hlwb los ntawm kev tsom ATG14, tus neeg tseem ceeb hauv kev tswj cov autophagy dependent phosphorylation ntawm beclin-1 [39]. Cov txiaj ntsig no tau qhia tias ntxiv rau apoptosis, induction ntawm lwm txoj kev tuag ntawm tes, autophagy, ntawm miRNA kuj tseem tuaj yeem ncua cyst loj hlob hauv ADPKD.

4.1.6. miR-214 

Interstitial o thiab fibrosis tshwm sim los ntawm tsub zuj zuj ntawm cov hlwb inflammatory yog ib qho ntawm cov yam ntxwv tseem ceeb ntawm PKD [76]. miR-214 yog muab los ntawm lncRNA, dynamin 3 opposite strand (DNM3OS). miR-214 tau raug tshaj tawm los ua lub luag haujlwm tseem ceeb hauv kev kho cov qog microenvironment los ntawm kev tswj cov kab mob inflammatory [77]. Ob leeg miR-214 thiab DNM3OS yog upregulated nyob rau hauv cystic ob lub raum los ntawm Pkd1 thiab Pkd2 nas qauv, thiab tib neeg ADPKD, tshwj xeeb tshaj yog nyob rau hauv interstitial hlwb nyob rau hauv lub cyst microenvironment [40]. Txawm li cas los xij, kev tshem tawm ntawm miR-214 hauv Pkd1 lossis Pkd2 tus qauv nas ua rau lub cyst loj hlob. Kev nthuav qhia ntawm pro-inflammatory TLR4 thiab tsub zuj zuj ntawm pericystic macrophages tau pom nyob rau hauv PKD nas qauv nrog miR-214 tshem tawm [40]. TLR4/IFN- /STAT1 transcriptionally activates qhov kev qhia ntawm DNM3OS, lub miR{22}} host gene. Ntawm qhov tod tes, miR-214 ncaj qha lub hom phiaj TLR4 thiab thim nws qhov kev xav los ua ib qho kev tawm tswv yim tsis zoo [40]. Txoj kev tshawb no tau qhia tias kev txhim kho ntawm miR-214 nyob rau hauv lub cyst microenvironment muaj kev tiv thaiv kev tiv thaiv ntawm inhibiting cyst kev loj hlob thiab interstitial o.

4.1.7 ib. miR-192, miR-194, thiab miR-30

Epithelial-mesenchymal hloov pauv (EMT) yog txheej txheem los ntawm cov hlwb epithelial hloov mus rau hauv cov hlwb mesenchymal, uas ua rau lub raum fibrosis hauv cov kab mob raum ntev [78]. EMT tau tshaj tawm tias muaj feem cuam tshuam nrog cyst expansion hauv PKD [79]. Los ntawm genome-wide tsom xam ntawm miRNA qhia thiab DNA methylation xwm txheej nyob rau hauv kawg-theem ADPKD, miR-192, thiab miR-194 tau pom tias yuav downregulated vim hypermethylation [41]. Lub downregulated miR-192 thiab miR-194 tau pom los pab rau EMT los ntawm kev cuam tshuam ncaj qha ntawm ZEB2 thiab CDH2 hauv ADPKD [41]. Kev kho nrog cov neeg ua ntej ntawm miR-192 thiab miR{13}} qeeb cyst loj hlob hauv Pkd1fox/flox: Aqp2-Cre nas [41]. Ntxiv mus, Magayr et al. tau txheeb xyuas ob lub raum-enriched neeg sib tw miRNA tsev neeg (miR{18}}/miR{19}} thiab miR-30) los ntawm profiling human urinary exosome miRNA los ntawm lub ntiaj teb me RNA sequencing los ntawm cov theem pib thiab lig ntawm ADPKD [ 42] ib. Tsib miRNAs los ntawm ob tsev neeg no, suav nrog miR-192-5p, miR-194-5p, miR-30a-5p, miR-30d-5 p, thiab miR-30e-5p, tau lees paub tias yuav raug txo qis hauv ADPKD cov neeg mob zis exosomes, thiab lub raum cystic los ntawm Pkd1 mutant nas thiab ADPKD cov neeg mob [42]. Cov yam tseem ceeb loj hlob / receptor tyrosine kinases (RTKs), Notch, Wnt / -catenin, thiab TGF- kev taw qhia txoj hauv kev tau kwv yees tias yuav cuam tshuam los ntawm cov kev txo qis miRNAs. PIK3R1 thiab ANO1 raug txheeb xyuas tias yog lub hom phiaj tshiab ntawm miR-194-5p, uas tau nce hauv ADPKD thiab txhawb kev loj hlob cyst. Tsis tas li ntawd, cov txheej txheem ntawm cov zis exosomal miRNAs no tuaj yeem ua cov biomarkers tshiab rau kev kis kab mob raws li tag nrho tsib miRNAs pom muaj kev sib raug zoo nrog lub hauv paus eGFR thiab ultrasound-txiav txim siab lub raum ntev [42].

4.1.8 ib. miR-193b-3p

Los ntawm kev sib piv cov miRNA profile hauv tib neeg lub cev thiab ADPKD hlwb, kaum tsib miRNAs tau sib txawv ntau dua ob npaug hauv ADPKD hlwb [43]. Ntawm lawv, miR- 193b-3p, cov qog nqaij hlav, yog downregulated nyob rau hauv tib neeg ADPKD hlwb, uas ua rau muaj kev nce nyob rau hauv kev qhia ntawm nws lub hom phiaj, EGF/ErbB tsev neeg receptor ErbB4 [43,80 ]. Ligand-induced activation ntawm ErbB4 txhawb cyst expansion los ntawm kev tsav cystic cell proliferation hauv ADPKD [43].

4.1.9 ib. miR-501-5p

Lub luag haujlwm ntawm p53 thiab mTOR kev taw qhia txoj hauv kev hauv PKD tau kawm dav [7,81,82]. miR-501-5p yog upregulated nyob rau hauv ADPKD hlwb thiab cov ntaub so ntswg, uas tswj cyst loj hlob los ntawm p53 thiab mTOR signaling txoj kev [44]. miR-501-5p txwv qhov kev qhia ntawm PTEN thiab TSC1, uas ua rau kev ua kom mTOR kinase [44]. Lub tshuab txais mTOR signaling txhawb p53 ubiquitination tshuaj los ntawm MDM2 [44]. Yog li, inhibition ntawm miR-501-5p txo cov cell proliferation thiab induces apoptosis los ntawm inactivation ntawm mTOR thiab restores p53 muaj nuj nqi nyob rau hauv ADPKD hlwb.

4.1.10 Nws. miR-182-5p, miR-20b-5p, thiab miR-106a-5p

miR-182-5p tau raug txheeb xyuas tias yog ib qho ntawm 13 qhov sib txawv ntawm miRNAs hauv lub raum los ntawm Pkd1fllox/fllox: HoxB7-Cre nas uas muaj cai tshem tawm Pkd1 hauv cov ducts sau [45]. Lub upregulated miR-182-5p tswj actin cytoskeleton rearrangement los ntawm repressing nws lub hom phiaj noob, Wasf2, Dock1, thiab Itga4, tawm tswv yim tias miR-182-5p-mediated defects ntawm actin cytoskeleton txhawb cyst kev loj hlob [45]. Peb txoj kev tshawb fawb tsis ntev los no tau pom tias p68, ib qho RNA helicase, txhawb kev qhia thiab kev loj hlob ntawm miR-17, miR-200c, thiab miR-182-5p, thiab ntxiv inhibited kev qhia ntawm Pkd1 [83 ]. Nws kuj tau tshaj tawm tias miR-20b-5p thiab miR-106a-5p yog downregulated nyob rau hauv lub raum los ntawm Pkd2flflox/fllox: HoxB7-Cre nas uas muaj ib qho kev rho tawm ntawm Pkd2 hauv cov kav dej sau [46]. Qhov txo qis miR-20b-5p thiab miR-106a-5p ua rau muaj kev txhim kho ntawm lawv lub hom phiaj, qhov zoo li Kruppel (Klf12), uas txhawb nqa kev loj hlob ntawm cyst los ntawm kev loj hlob ntawm tes [46]

4.1.11. LnRNAs hauv ADPKD

Cov dysregulated lncRNAs hauv Pkd1flflox/flox: Ksp-Cre nas thiab Pkd2flflox/flox: Pkhd1-Cre nas raug txheeb xyuas los ntawm sib sib zog nqus RNA-seq, uas 139 lncRNAs yog dysregulated nyob rau hauv Pkd1 conditional knockouts 6 lub raum Pkd2 conditional knockout ob lub raum [84]. Qhov kev qhia ntawm 50 qhov tshwj xeeb lncRNAs hloov ntau dua ob npaug ntawm Pkd1 thiab Pkd2 nas qauv. Ntawm cov feem ntau dysregulated lncRNAs, Hoxb3os yog evolutionarily kev txuag thiab qhia heev nyob rau hauv lub raum cov ntaub so ntswg, uas yog downregulated nyob rau hauv ob lub raum los ntawm Pkd1 thiab Pkd2 conditional knockout nas. Kev nthuav qhia ntawm tib neeg ortholog HOXB3-AS1 txo qis hauv ob lub raum ntawm cov neeg mob ADPKD. Knockout ntawm Hoxb3os nyob rau hauv mIMCD3 hlwb los ntawm CRISPR/Cas9 activates lub phosphorylation ntawm mTOR thiab nws downstream lub hom phiaj, xws li p70 S6 kinase, ribosomal protein S6, thiab cov txhais lus repressor 4E-BP1. Lub mIMCD3 hlwb nrog Hoxb3os deletion tau nce mitochondrial ua pa, uas zoo ib yam nrog rau kev ua kom lub mTOR signaling pathway [84]. Cov kev tshawb pom no qhia tias kev txo qis ntawm Hoxb3os yuav yog los ntawm kev ua kom mTOR thiab cov metabolism hauv mitochondrial los txhawb kev loj hlob ntawm cyst hauv ADPKD.

4.2. miRNAs hauv Autosomal Recessive Polycystic raum Kab Mob (ARPKD)

ARPKD yog tshwm sim los ntawm kev hloov pauv ntawm PKHD1 noob thiab yog tus cwj pwm los ntawm lub raum loj thiab congenital hepatic fibrosis [85]. Nws tau raug tshaj tawm tias miRNAs kuj tseem txhawb nqa cov kab mob ntawm ARPKD. Ua ntej, qhov kev qhia ntawm PKHD1 yog post-transcriptionally negatively tswj los ntawm miR-365-1 [86]. Qhov thib ob, qhov kev txo qis ntawm cov kab mob epithelial sodium channel (ENaC) kho los ntawm miR-9a-5p, uas tau tswj hwm hauv kev sau cov kab hluav taws xob, pab txhawb kom ncua kev loj hlob ntawm cov cyst hauv cov ntsev tsis muaj zaub mov noj PCK nas. , ARPKD qauv [47].

Lub luag haujlwm ntawm miRNA hauv cov kab mob siab polycystic (PLDs) kuj tau tshawb xyuas hauv PCK nas. Cov theem qhia ntawm miR-15a yog downregulated nyob rau hauv cholangiocyte cell kab PCK-CCL thiab cystic daim siab cov ntaub so ntswg los ntawm PCK nas, thiab nyob rau hauv cov neeg mob nrog ib tug PLD [48]. Downregulation ntawm miR-15ua kom ceev cholangiocyte cell proliferation thiab txhawb lub siab cyst loj hlob los ntawm upregulation ntawm nws lub hom phiaj, cell-cycle regulator cell division cycle 25A (Cdc25a) [48].

5. miRNAs hauv HNF1 -Associated Kidney Disease

HNF1 yog DNA-binding transcription yam uas tswj cov kev qhia ntawm cov noob koom nrog hauv kev thauj cov membrane, cell sib txawv, thiab cov metabolism hauv lub raum tubular epithelial hlwb [87]. Kev hloov pauv hauv HNF1B hauv tib neeg ua rau muaj ntshav qab zib mature ntawm cov hluas, hom 5 (MODY5), cystic raum kab mob, multicystic dysplastic ob lub raum, glomeruli cystic raum kab mob, autosomal dominant tubulointerstitial raum kab mob, thiab congenital anomalies ntawm lub raum thiab urinary tract ( QAB) [56]. HNF1 yog qhia nyob rau hauv nephrons thiab branching ureteric bud thaum lub raum kev loj hlob. HNF1 yog qhia tsis tu ncua nyob rau hauv lub raum tubular epithelial hlwb, tab sis tsis nyob rau hauv glomeruli los yog interstitium ntawm lub raum laus. Raws li ib qho tseem ceeb transcriptional regulator, HNF1 yuav tsum tau rau ntau kauj ruam ntawm lub raum txoj kev loj hlob, xws li ureteric bud branching, pib ntawm nephrogenesis, thiab nephron segmentation [87]. Cov xwm txheej knockout ntawm Hnf1b hauv nas raum ua rau lub raum cyst kev loj hlob thiab lub raum tsis ua haujlwm. HNF1 tswj cov kev hloov pauv ntawm ntau yam kab mob cystic noob, suav nrog PKD2, PKHD1, UMOD, thiab GLIS2 [87]. UMOD yog txuam nrog medullary cystic raum kab mob, thiab GLIS2 yog txuam nrog nephronophthisis. Rau lub luag haujlwm ncaj qha hauv kev hloov pauv ntawm PKD2 thiab PKHD1, HNF1 tau lees paub tias yog tus hloov pauv hauv PKD, txawm hais tias kev hloov pauv hauv HNF1B tsis ua rau muaj kab mob polycystic raum [56]. Kev hloov pauv ntawm HNF1B kuj ua rau muaj kev cuam tshuam electrolyte, suav nrog hypomagnesemia thiab hypokalemia. HNF1 tswj cov hlau thauj mus rau hauv lub raum los ntawm kev cuam tshuam rau kev nthuav qhia ntawm cov khoom thauj mus los ntawm nephron. HNF1 kuj tseem tswj hwm cov lus qhia ntawm FXYD2 uas encodes subunit ntawm Na plus -K plus -ATPase. Kev hloov pauv ntawm FXYD2 ua rau hypomagnesemia. Nws tau raug pom zoo tias qhov txo qis hauv cov tshuaj magnesium concentration ua rau cov zis potassium nkos los ntawm kev tso tawm ntawm inhibition ntawm lub raum sab nrauv medullary K ntxiv channel (ROMK) [88]. Tsis tas li ntawd, HNF1 tuaj yeem tswj hwm qhov kev hloov pauv ntawm UMOD, SCL12A1, thiab KCNJ10, uas encode uromodulin, Na plus -K plus -Cl- transporter (NKCC2), thiab K ntxiv channel Kir5.1, raws li, thiab koom nrog rau hauv lub raum poov tshuaj tuav. [87].

Cov miRNAs uas ncaj qha tswj hwm los ntawm HNF1 hauv lub raum epithelial hlwb tau txheeb xyuas los ntawm ChiP-seq nrog microarray tsom [89]. Tsev neeg miR-200, suav nrog miR- 200b/200a/429, yog lub hom phiaj hloov pauv ntawm HNF1 hauv lub raum epithelial hlwb. Knockout ntawm HNF1 txo qis kev qhia ntawm miR-200 thiab nce qhov kev qhia ntawm miR-200 lub hom phiaj, suav nrog Zeb2 thiab Pkd1 hauv HNF1 knockout nas ob lub raum, txhawb nqa tias HNF-1 tswj EMT thiab cystic raum kab mob ntawm repressing qhov qhia ntawm miR-200 (Daim duab 3). Tsis tas li ntawd, kev hloov pauv ntawm HNF-1 txo cov ntshav qab zib ntawm plaub miRNAs, suav nrog miR-24, miR-27b, miR-223, thiab miR-199a , hauv MODY5 cov neeg mob piv rau tag nrho lwm cov neeg mob ntshav qab zib thiab cov neeg noj qab haus huv hauv Polish pawg [90]. HNF-1, ntawm qhov tod tes, tuaj yeem raug tswj hwm los ntawm miRNAs hauv lub raum thiab lub siab (Daim duab 3). Nws tau pom tias HNF-1 raug tswj tsis zoo los ntawm miR{28}} hauv cystic raum epithelial hlwb [33]. HNF-1 raug txwv los ntawm miR-194 los ntawm kev khi rau ntawm qhov chaw khaws cia miR-194 khi nyob rau hauv 30 -UTR ntawm HNF-1 , ua rau txo qis cell proliferation thiab txhawb nqa cell apoptosis thiab tsiv teb tsaws ntawm nas metanephric mesenchyme (MM) hlwb [91]. Lub 30 -UTR ntawm HNF-1 kuj muaj qhov chaw khaws cia miR-802 khi qhov chaw. Kev nthuav qhia ntawm miR-802 yog nce nyob rau hauv daim siab ntawm cov rog rog qauv thiab tib neeg cov kev rog, uas yuav txo tau qhov kev qhia ntawm HNF-1 nyob rau hauv lub siab, ua rau cov piam thaj intolerance, impaired insulin signaling, thiab nce siab gluconeogenesis [92].

6. miRNAs hauv Alport Syndrome

Qhov kev qhia miR-21 yog siab dua hauv tubulointerstitium ntawm ob lub raum los ntawm cov nas qus [95]. Txawm li cas los xij, qib miR-21 hauv lub glomeruli yog upregulated nyob rau hauv lub raum ntawm Col4 3 −/− nas, ib tug murine qauv ntawm Alport syndrome [95]. Qhov kev qhia ntawm miR-21 nyob rau hauv ob lub raum ntawm cov neeg mob Alport syndrome tau nce ntau dua piv rau tib neeg lub raum tswj [96]. Tshwj xeeb, miR-21 tau qhia ntau heev nyob rau hauv lub cev puas hlwb epithelial thiab glomeruli. Cov qib siab ntawm miR-21 cuam tshuam nrog cov kab mob hnyav ntsuas los ntawm cov proteinuria, lub raum ua haujlwm, thiab cov qhab nia ntawm lub raum histopathology [96].

Lub luag haujlwm ua haujlwm ntawm miR-21 hauv lub raum fibrosis tau tshawb xyuas ntau yam hauv ntau yam nephropathies [65]. miR-21 pab txhawb rau lub raum fibrogenesis los ntawm kev ntsiag to metabolic txoj hauv kev, tshwj xeeb kho los ntawm nws lub hom phiaj, PPAR , thiab mitochondrial inhibitor ntawm reactive oxygen hom tiam Mpv17l hauv unilateral ureteral obstruction qauv [97]. Cov tshuaj tiv thaiv-miR-21 oligonucleotides yog tshuaj hloov kho ib leeg-stranded RNA molecules nrog tag nrho cov sequence complementarity rau miR-21. Kev kho mob nrog cov tshuaj tiv thaiv-miR-21 oligonucleotides txo glomerulosclerosis, interstitial fibrosis, tubular raug mob, thiab mob, thiab yog li ntawd txhim kho txoj sia nyob ntawm Col4 3 −/- nas [95]. Lub hom phiaj ntawm miR-21 qhib PPAR / retinoid X receptor (PPAR / RXR) thiab nws cov kev taw qhia hauv qab hauv podocytes, tubular, thiab interstitial hlwb (Daim duab 4) [95]. Kev kho mob nrog anti-miR-21 oligonucleotides kuj tau txhim kho mitochondrial muaj nuj nqi los ntawm kev txo cov mitochondrial ROS ntau lawm [95]. Raws li kev tiv thaiv kev tiv thaiv lub raum fibrosis thiab o ntawm anti-miR-21 oligonucleotides hauv Col4 3 −/- nas qauv, Phase 2, randomized, ob-dig muag, tshuaj placebo-tswj tshuaj (ClinicalTrials .gov identifier NCT02855268) los soj ntsuam kev nyab xeeb, kev ua tau zoo, pharmacodynamics, thiab pharmacokinetics ntawm anti-miR-21 tus neeg sawv cev RG-012 hauv cov neeg mob Alport syndrome tab tom ua [98].

Tsis tas li ntawd, nrog RNA-seq tsom xam los qhia qhov qhia ntawm miRNAs hauv induced pluripotent qia hlwb (iPSCs) tsim los ntawm lub raum tubular hlwb ntawm cov neeg mob Alport syndrome thiab kev tswj ib txwm [99], 155 qhov sib txawv qhia miRNAs tau raug txheeb xyuas. Ntawm cov miRNAs, has-mir-4651, has-mir-4461, thiab has-miR-4775 tau lees paub tias yuav raug kho nyob rau hauv iPSCs los ntawm cov neeg mob uas muaj Alport syndrome [99], tawm tswv yim Lub luag haujlwm ntawm cov miRNAs hauv Alport syndrome.

7. miRNAs nyob rau hauv Congenital Abnormalities ntawm lub raum thiab Urinary Tract (CAKUT)

CAKUT muaj qhov dav phenotypic spectrum ntawm kev loj hlob tsis xws luag [100]. Cov phenotypes ntawm CAKUT muaj xws li lub raum agenesis thiab hip dysplasia, cystic raum kab mob, dysplastic raum, hydronephrosis, ureteropelvic junction obstruction, ureter malformations, thiab vesicoureteral reflux. CAKUT suav txog kwv yees li 50 feem pua ​​​​ntawm cov neeg mob hauv lub raum kawg [100]. Tsawg dua 18 feem pua ​​​​ntawm CAKUT mob yog tshwm sim los ntawm kev tsim cov kev hloov pauv monogenic [101]. Ib qho kev hloov pauv ib leeg los ntawm kwv yees li 40 cov noob sib txawv (25 qhov tseem ceeb thiab 15 recessives) tau raug txheeb xyuas tias ua rau CAKUT [101]. Lub koom haum ntawm miRNAs nrog CAKUT-ua rau cov noob tsis yog lub hom phiaj ntawm qhov kev tshuaj xyuas no tab sis tau raug tshuaj xyuas los ntawm Marrone li al. [102]. Ntau yam ntawm CAKUT-ua rau cov noob encode transcription yam uas ua lub luag haujlwm tseem ceeb hauv nephrogenesis, xws li HNF1B, PAX2, thiab FOXC1. MicroRNAs yog ib qho tseem ceeb regulators ntawm noob qhia los ntawm kev khi ncaj qha nrog mRNA 30 -UTR ntawm lub hom phiaj noob, xws li cov miR-92 thiab miR-194 ntawm HNF1B, qhia txog lub luag haujlwm ntawm microRNAs hauv CAKUT .

Genetic deletion ntawm microRNA-processing Dicer hauv kev tsim lub raum tubules thiab ureteric buds ua rau lub raum tsis ua haujlwm thiab tsiaj tuag thaum muaj hnub nyoog 4-6 lub lis piam [103]. Cov phenotypes ntawm Dicer knockout nas muaj xws li ob lub raum me me vim qhov txo qis ntawm nephrons thiab hydronephrosis vim ureteropelvic junction obstruction. Lub raum hypoplasia yog tshwm sim los ntawm kev txo qis hauv tubular branching, thiab cov anomalies ntawm ureters nyob rau hauv ob lub raum tshwm sim los ntawm ib tug tsis xws luag nyob rau hauv qhov sib txawv ntawm ureteric du leeg hlwb hauv Dicer knockout nas [103]. Tsis tas li ntawd, kev kho mob ntawm lwm qhov tseem ceeb ntawm miRNA-processing enzyme (Dgcr8) nyob rau hauv lub distal nephrons thiab ureteric buds ua rau mob hnyav hydronephrosis, raum cyst, mob raum tsis ua haujlwm, thiab tuag ntxov ntxov, uas zoo li phenotype ntawm Dicer knockout nas [104]. Cov txiaj ntsig tau pom tias lub luag haujlwm tseem ceeb ntawm microRNA-dependent gene regulation hauv lub raum kev loj hlob. Yog li, dysregulation lossis kev hloov pauv ntawm miRNAs yuav yog qhov ua rau CAKUT. Tsis tas li ntawd, xya miRNAs raug txheeb xyuas los cuam tshuam nrog CAKUT los ntawm kev sib koom ua ke ntawm microarray noob qhia thiab miRNA lub hom phiaj kev kwv yees ntawm cov qauv ureter los ntawm cov neeg mob CAKUT cov neeg mob thiab tswj cov tib neeg [105]. Kev qhia theem ntawm hsa-miR-144 tau nce mus txog 5.7-fold nce hauv ureter cov ntaub so ntswg los ntawm CAKUT cov neeg mob. Lub luag haujlwm ua haujlwm ntawm hsa-miR-144 hauv CAKUT yuav tsum tau tshawb xyuas ntxiv. Tsis tas li ntawd, los ntawm kev sib txuas ntawm 96 qia-loop cheeb tsam ntawm 73 lub raum kev loj hlob miRNA noob nyob rau hauv cov tib neeg uas tsis yog-syndromic CAKUT, ob miRNAs (MIR19B1 thiab MIR99A) tau txheeb xyuas nrog cov kab mob sib txawv hauv ob ntawm 1213 tus neeg tsis sib xws.

8. Noncoding RNA hauv VHL Kab Mob

Tus kab mob VHL yog ib qho autosomal dominant hereditary syndrome, uas yog tus cwj pwm los ntawm kev loj hlob ntawm benign thiab malignant qog nyob rau hauv ntau lub cev [107]. Tus kab mob VHL yog tshwm sim los ntawm germline mutations ntawm VHL noob, ib tug qog suppressor noob. Cov qog nqaij hlav hauv tus kab mob VHL muaj xws li retinal hemangioblastomas, pheochromocytomas, lub raum hlwv, thiab lub raum cell carcinoma (ccRCC). Kev ua haujlwm poob ntawm VHL noob, xws li somatic VHL hloov pauv thiab txhawb nqa hypermethylation, tau tshaj tawm nyob rau hauv feem ntau ntawm ccRCC [108]. VHL koom nrog cov protein ntau los tsim E3 ligase enzyme complex uas ubiquitinates hypoxia-inducible factor alpha (HIF) rau proteasomal degradation. Nrog rau qhov tsis muaj VHL, HIF accumulates nyob rau hauv lub cell thiab dimerizes nrog HIF los tsim HIF / complex, uas transcriptionally active ib tug series ntawm hypoxia- teb cov noob, nrog rau vascular endothelial kev loj hlob factor (VEGF), platelet-derived kev loj hlob yam (PDGF) , thiab lwm yam [108]. Cov kev taw qhia qis qis tau qhib los ntawm hypoxia- teb cov noob ua lub luag haujlwm tseem ceeb hauv cov qog nqaij hlav ntawm ccRCC.

Ntau cov kev tshawb fawb tau tsom mus rau microRNA qhia cov ntaub ntawv nyob rau hauv sporadic ccRCC thiab tau txheeb xyuas ntau yam oncogenic thiab oncosuppressive miRNAs thiab lncRNAs uas tswj cov kev taw qhia tseem ceeb ntawm ccRCC [109–111]. Txawm li cas los xij, ob peb tsab ntawv tshaj tawm txog tam sim no tau kawm txog lub luag haujlwm ntawm miRNAs hauv VHL-txuas nrog kev sib txuas ntawm ccRCC. Los ntawm kev txheeb xyuas miRNA thiab mRNA cov ntaub ntawv ntawm VHL-koom nrog ccRCC, sporadic ccRCC, thiab lub raum cov ntaub so ntswg [112], tag nrho ntawm 103 miRNAs tau sib txawv hauv cov qauv ccRCC piv rau cov ntaub so ntswg hauv lub raum. Ob feem peb ntawm miRNAs, suav nrog 12 upregulated thiab 56 downregulated miRNAs, feem ntau pom nyob rau hauv ob qho tib si hereditary thiab sporadic ccRCC pawg. 18 miRNAs tau hais txawv txawv hauv VHL-txuas nrog ccRCC piv rau cov nyob hauv ccRCC tsis sib xws. Cov kev qhia ntawm miR-210 thiab miR{12}} yog upregulated nyob rau hauv ob qho tib si VHL-koom nrog thiab sporadic ccRCC. MiR-210 tau tshaj tawm los tswj cov cellular hypoxic teb, lub voj voog ntawm tes, mitochondrial oxidative metabolism, thiab angiogenesis hauv ntau hom qog nqaij hlav [113]. miR-155 tau tshaj tawm los txhawb cov qog loj hlob los ntawm kev txo qis VHL mRNA thiab HIF1 kev ua haujlwm thaum lub sijhawm ntev hypoxia [114,115]. miR-30c-3p thiab miR-30a-3p yog downregulated nyob rau hauv ob qho tib si VHL-koom nrog thiab sporadic ccRCC, uas inhibit cell proliferation thiab angiogenesis los ntawm ncaj qha tsom HIF2 nyob rau hauv ccRCC [116].

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