title: Renal Vein Levels of MicroRNA-26a Are Lower in the Poststenotic Kidney.
abstract: MicroRNA-26a (miR-26a) is a post-transcriptional regulator that inhibits cellular differentiation and apoptosis. Renal vascular disease (RVD) induces ischemic injury characterized by tubular cell apoptosis and interstitial fibrosis. We hypothesized that miR-26a levels are reduced in the poststenotic kidney and that kidney repair achieved by adipose tissue-derived mesenchymal stem cells (ad-MSCs) is associated with restored miR-26a levels. Renal function and renal miR-26a levels were assessed in pigs with RVD not treated (n=7) or 4 weeks after intrarenal infusion of ad-MSC (2.5×10(5) cells/kg; n=6), patients with RVD (n=12) or essential hypertension (n=12), and healthy volunteers (n=12). In addition, the direct effect of miR-26a on apoptosis was evaluated in a renal tubular cell culture. Compared with healthy control kidneys, swine and human poststenotic kidneys had 45.5±4.3% and 90.0±3.5% lower levels of miR-26a, respectively, which in pigs, localized to the proximal tubules. In pigs, ad-MSC delivery restored tubular miR-26a expression, attenuated tubular apoptosis and interstitial fibrosis, and improved renal function and tubular oxygen-dependent function. In vitro, miR-26a inhibition induced proximal tubular cell apoptosis and upregulated proapoptotic protein expression, which were both rescued by ad-MSC. In conclusion, decreased tubular miR-26a expression in the poststenotic kidney may be responsible for tubular cell apoptosis and renal dysfunction but can be restored using ad-MSC. Therefore, miR-26a might be a novel therapeutic target in renovascular disease.
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: John R
authors.initials: JR
authors.lastname: Woollard
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Michael
authors.initials: M
authors.lastname: Ofori
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Saad
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Sandra M S
authors.initials: SM
authors.lastname: Herrmann
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: Divisions of Nephrology and Hypertension and.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
authors.affiliation: Cardiovascular Diseases and.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: Divisions of Nephrology and Hypertension and Cardiovascular Diseases and lerman.lilach@mayo.edu.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000473:pathology / Q000628:therapy; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D035683:MicroRNAs / Q000097:blood*; D012016:Reference Values; D012078:Renal Artery Obstruction / Q000097:blood* / Q000473:pathology / Q000628:therapy; D012082:Renal Veins / Q000378:metabolism*; D012720:Severity of Illness Index; D013552:Swine; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs
keywords: kidney; microRNA; renal artery stenosis; stem cell