TY - JOUR
T1 - Renal vein levels of MicroRNA-26a are lower in the poststenotic kidney
AU - Zhu, Xiang Yang
AU - Ebrahimi, Behzad
AU - Eirin, Alfonso
AU - Woollard, John R.
AU - Tang, Hui
AU - Jordan, Kyra L.
AU - Ofori, Michael
AU - Saad, Ahmed
AU - Herrmann, Sandra M.S.
AU - Dietz, Allan B.
AU - Textor, Stephen C.
AU - Lerman, Amir
AU - Lerman, Lilach O.
N1 - Publisher Copyright:
Copyright © 2015 by the American Society of Nephrology.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2014030248
DO - 10.1681/ASN.2014030248
M3 - Article
C2 - 25270070
AN - SCOPUS:84930437267
SN - 1046-6673
VL - 26
SP - 1378
EP - 1388
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 6
ER -