Inhibition of miR-29 by TGF-beta-Smad3 signaling through dual mechanisms promotes transdifferentiation of mouse myoblasts into myofibroblasts

• Published in: PloS one Vol. 7; no. 3; p. e33766
• Main Authors: Zhou, Liang, Wang, Lijun, Lu, Leina, Jiang, Peiyong, Sun, Hao, Wang, Huating
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.03.2012; Public Library of Science (PLoS)
• Subjects: Animals; Base Sequence; Biological activity; Biology; Bone morphogenetic proteins; Cell adhesion; Cell cycle; Cell growth; Cell Line; Cell Transdifferentiation - genetics; Cell Transdifferentiation - physiology; Clinical trials; Differentiation; Down-Regulation; Extracellular matrix; Gene expression; Gene sequencing; Genes; Genetic aspects; Gynecology; Health sciences; Hypertension; Hypotheses; Kinases; Medicine; Mice; MicroRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Models, Biological; Muscles; Muscular dystrophy; Musculoskeletal system; Myoblasts; Myoblasts, Skeletal - cytology; Myoblasts, Skeletal - metabolism; MyoD protein; MyoD Protein - metabolism; Myofibroblasts - cytology; Myofibroblasts - metabolism; Myogenesis; Obstetrics; Pathogenesis; Pathology; Polycomb group proteins; Post-transcription; Promoter Regions, Genetic; Proteins; Repressor Proteins - metabolism; Ribonucleic acid; RNA; RNA, Small Interfering - genetics; Rodents; Signal Transduction - physiology; Signaling; Smad3 protein; Smad3 Protein - antagonists & inhibitors; Smad3 Protein - genetics; Smad3 Protein - metabolism; Transcription (Genetics); Transcriptome; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Transforming growth factors; Trends; YY1 Transcription Factor - metabolism; Hong Kong China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033766

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in regulating many biological processes, including myogenic differentiation and muscle development. miR-29 is a promoting factor during myogenesis but its full spectrum of impact on muscle cells has yet to be explored. Here we describe an analysis of miR-29 affected transcriptome in C2C12 muscle cells using a high throughput RNA-sequencing platform. The results reveal that miR-29 not only functions to promote myogenic differentiation but also suppresses the transdifferentiation of myoblasts into myofibroblasts. miR-29 inhibits the fibrogenic differentiation through down-regulating both extracellular matrix genes and cell adhesion genes. We further demonstrate that miR-29 is under negative regulation by TGF-beta (TGF-β)-Smad3 signaling via dual mechanisms of both inhibiting MyoD binding and enhancing Yin Yang 1 (YY1)-recruited Polycomb association. Together, these results identify miR-29 as a pleiotropic molecule in both myogenic and fibrogenic differentiation of muscle cells.