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

Cell Death Dis. 2015 Dec 3;6(12):e2011. doi: 10.1038/cddis.2015.353.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / cytology
  • Intestines / pathology
  • Mice
  • MicroRNAs / metabolism*
  • Myocytes, Smooth Muscle
  • Serum Response Factor / metabolism*
  • Signal Transduction

Substances

  • MicroRNAs
  • Serum Response Factor