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Author Notes:

Correspondence: Dr. Xiaonan Wang, Renal Division, Emory University, School of Medicine, M/S 1930/001/1AG, 1639 Pierce Drive, WMB 338, Atlanta, Georgia 30322. Phone: 404-727-1798. Fax: 404-727-3425. Email: xwang03@emory.edu.

We thank Dr. Huating Wang for kindly providing the pLuc-3UTRmutant-YY1 vector.

There are no conflicts of interest to disclose.

Subjects:

Research Funding:

This work was supported in part by the University Research Committee of Emory University and Norman S. Coplon extramural research grants from Satellite Health Research to both X.H.W. and L.Z.

Additional support was NIH DK062081 to J.D.K. and NIH R37 DK37175 to W.E.M. and the Virology & Drug Discovery Core of the Emory Center for AIDS Research (P30 AI050409).

Decreased miR-29 Suppresses Myogenesis in CKD

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Journal Title:

Journal of the American Society of Nephrology

Volume:

Volume 22, Number 11

Publisher:

, Pages 2068-2076

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The mechanisms underlying the muscle wasting that accompanies CKD are not well understood. Animal models suggest that impaired differentiation of muscle progenitor cells may contribute. Expression of the myogenesis-suppressing transcription factor Ying Yang-1 increases in muscle of animals with CKD, but the mechanism underlying this increased expression is unknown. Here, we examined a profile of microRNAs in muscles from mice with CKD and observed downregulation of both microRNA-29a (miR-29a) and miR-29b. Because miR-29 has a complementary sequence to the 3′-untranslated region of Ying Yang-1 mRNA, a decrease in miR-29 could increase Ying Yang-1. We used adenovirus-mediated gene transfer to express miR-29 in C2C12 myoblasts and measured its effect on both Ying Yang-1 and myoblast differentiation. An increase in miR-29 decreased the abundance of Ying Yang-1 and improved the differentiation of myoblasts into myotubes. Similarly, using myoblasts isolated from muscles of mice with CKD, an increase in miR-29 improved differentiation of muscle progenitor cells into myotubes. In conclusion, CKD suppresses miR-29 in muscle, which leads to higher expression of the transcription factor Ying Yang-1, thereby suppressing myogenesis. These data suggest a potential mechanism for the impaired muscle cell differentiation associated with CKD.

Copyright information:

© 2011 by the American Society of Nephrology

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