title: Decreased miR-29 suppresses myogenesis in CKD.
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.
authors.affiliation: Renal Division, Emory University, School of Medicine, Atlanta, Georgia 30322, USA. xwang03@emory.edu
authors.forename: Xiaonan H
authors.initials: XH
authors.lastname: Wang
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.forename: William E
authors.initials: WE
authors.lastname: Mitch
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D024510:Muscle Development / Q000502:physiology*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D050986:YY1 Transcription Factor / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse