Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells

C. Park, M. Y. Lee, O. J. Slivano, P. J. Park, S. Ha, R. M. Berent, R. Fuchs, N. C. Collins, T. J. Yu, H. Syn, J. K. Park, K. Horiguchi, J. M. Miano, K. M. Sanders, S. Ro

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Serum response factor (SRF) is a transcription factor known to mediate phenotypic plasticity in smooth muscle cells (SMCs). Despite the critical role of this protein in mediating intestinal injury response, little is known about the mechanism through which SRF alters SMC behavior. Here, we provide compelling evidence for the involvement of SRF-dependent microRNAs (miRNAs) in the regulation of SMC apoptosis. We generated SMC-restricted Srf inducible knockout (KO) mice and observed both severe degeneration of SMCs and a significant decrease in the expression of apoptosis-associated miRNAs. The absence of these miRNAs was associated with overexpression of apoptotic proteins, and we observed a high level of SMC death and myopathy in the intestinal muscle layers. These data provide a compelling new model that implicates SMC degeneration via anti-apoptotic miRNA deficiency caused by lack of SRF in gastrointestinal motility disorders.

Original languageEnglish (US)
Article numbere2011
JournalCell Death and Disease
Volume6
DOIs
StatePublished - Dec 3 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Park, C., Lee, M. Y., Slivano, O. J., Park, P. J., Ha, S., Berent, R. M., Fuchs, R., Collins, N. C., Yu, T. J., Syn, H., Park, J. K., Horiguchi, K., Miano, J. M., Sanders, K. M., & Ro, S. (2015). Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells. Cell Death and Disease, 6, [e2011]. https://doi.org/10.1038/cddis.2015.353