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 Herrmann, Allan B Dietz, Stephen C Textor, Amir Lerman, Lilach O Lerman

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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 (2.5×10<sup>5</sup> 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

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ASJC Scopus subject areas

  • Nephrology

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