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

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

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Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
Department of Physiology, Wonkwang Digestive Disease Research Institute and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan, Jeollabuk-do, Korea.
Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Division of Biological Science, Wonkwang University, Iksan, Jeollabuk-do, Korea.
Department of Anatomy, University of Fukui Faculty of Medical Sciences, Matsuoka, Fukui, Japan.


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.

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