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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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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Renal Veins
MicroRNAs
Kidney
Mesenchymal Stromal Cells
Adipose Tissue
Apoptosis
Swine
Vascular Diseases
Fibrosis
Healthy Volunteers

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal vein levels of MicroRNA-26a are lower in the poststenotic kidney. / Zhu, Xiang Yang; Ebrahimi, Behzad; Eirin, Alfonso; Woollard, John R.; Tang, Hui; Jordan, Kyra L.; Ofori, Michael; Saad, Ahmed; Herrmann, Sandra; Dietz, Allan B; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O.

In: Journal of the American Society of Nephrology, Vol. 26, No. 6, 01.06.2015, p. 1378-1388.

Research output: Contribution to journalArticle

Zhu, Xiang Yang ; Ebrahimi, Behzad ; Eirin, Alfonso ; Woollard, John R. ; Tang, Hui ; Jordan, Kyra L. ; Ofori, Michael ; Saad, Ahmed ; Herrmann, Sandra ; Dietz, Allan B ; Textor, Stephen C ; Lerman, Amir ; Lerman, Lilach O. / Renal vein levels of MicroRNA-26a are lower in the poststenotic kidney. In: Journal of the American Society of Nephrology. 2015 ; Vol. 26, No. 6. pp. 1378-1388.
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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.",
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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

AU - Dietz, Allan B

AU - Textor, Stephen C

AU - Lerman, Amir

AU - Lerman, Lilach O

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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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