title: Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells.
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.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: C
authors.initials: C
authors.lastname: Park
authors.affiliation: 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.
authors.forename: M Y
authors.identifier: http://orcid.org/0000-0003-4956-9241
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: O J
authors.initials: OJ
authors.lastname: Slivano
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Park
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ha
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Berent
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fuchs
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Collins
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Yu
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: H
authors.initials: H
authors.lastname: Syn
authors.affiliation: Division of Biological Science, Wonkwang University, Iksan, Jeollabuk-do, Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Anatomy, University of Fukui Faculty of Medical Sciences, Matsuoka, Fukui, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Horiguchi
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Miano
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Sanders
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ro
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D026362:Serum Response Factor