Molecular mechanism of transforming growth factor-beta-mediated inhibition of growth arrest and differentiation in a myoblast cell line

作者: Masanori Murakami , Mizue Ohkuma , Masataka Nakamura

DOI: 10.1111/J.1440-169X.2007.00982.X

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摘要: Transforming growth factor-beta (TGF-beta) has been demonstrated to inhibit myogenesis in myoblasts. Here we report that transcriptional upregulation of p21(WAF1/Cip1) and muscle creatinine kinase (MCK) genes C2C12 cells, which are associated with arrest at the G1 phase representative cell-lineage-specific expression during myogenesis, was inhibited by TGF-beta treatment. cells expressed TWIST2, but not TWIST1, downregulated myogenic differentiation response low-serum cultures. We further found prevented differentiation-associated downregulation TWIST2 transcription, resulting maintaining mRNA as high growing cells. Ectopic suppressed p21 MCK promoters activated exogenous addition E2A MyoD this inhibitory effect cancelled introduction short hairpin RNA (shRNA) against TWIST2. On other hand, shRNA failed recover endogenous promoter activities from TGF-beta-mediated repression. The results clearly indicate inhibits maintains Our data however suggest signaling pathway may involve expression.

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