Renal vein levels of MicroRNA-26a are lower in the poststenotic kidney

Xiang Yang Zhu, Behzad Ebrahimi, Alfonso Eirin, John R. Woollard, Hui Tang, Kyra L. Jordan, Michael Ofori, Ahmed Saad, Sandra M.S. Herrmann, Allan B. Dietz, Stephen C. Textor, Amir Lerman, Lilach O. Lerman

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 (2.5×105 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.

Original languageEnglish (US)
Pages (from-to)1378-1388
Number of pages11
JournalJournal of the American Society of Nephrology
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Nephrology

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