title: MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
abstract: Smooth muscle cells (SMCs) express a unique set of microRNAs (miRNAs) which regulate and maintain the differentiation state of SMCs. The goal of this study was to investigate the role of miRNAs during the development of gastrointestinal (GI) SMCs in a transgenic animal model. We generated SMC-specific Dicer null animals that express the reporter, green fluorescence protein, in a SMC-specific manner. SMC-specific knockout of Dicer prevented SMC miRNA biogenesis, causing dramatic changes in phenotype, function, and global gene expression in SMCs: the mutant mice developed severe dilation of the intestinal tract associated with the thinning and destruction of the smooth muscle (SM) layers; contractile motility in the mutant intestine was dramatically decreased; and SM contractile genes and transcriptional regulators were extensively down-regulated in the mutant SMCs. Profiling and bioinformatic analyses showed that SMC phenotype is regulated by a complex network of positive and negative feedback by SMC miRNAs, serum response factor (SRF), and other transcriptional factors. Taken together, our data suggest that SMC miRNAs are required for the development and survival of SMCs in the GI tract.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Chanjae
authors.initials: C
authors.lastname: Park
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Sean M
authors.initials: SM
authors.lastname: Ward
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Wu
authors.forename: William J
authors.initials: WJ
authors.lastname: Hatton
authors.forename: Jong Kun
authors.initials: JK
authors.lastname: Park
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Seungil
authors.initials: S
authors.lastname: Ro
mesh_terms: D000818:Animals; D041981:Gastrointestinal Tract / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*
chemical_list: D035683:MicroRNAs