The RNA-binding protein RBPMS2 regulates development of gastrointestinal smooth muscle.

Details

Serval ID
serval:BIB_1307CA5EC49E
Type
Article: article from journal or magazin.
Collection
Publications
Title
The RNA-binding protein RBPMS2 regulates development of gastrointestinal smooth muscle.
Journal
Gastroenterology
Author(s)
Notarnicola C., Rouleau C., Le Guen L., Virsolvy A., Richard S., Faure S., De Santa Barbara P.
ISSN
1528-0012 (Electronic)
ISSN-L
0016-5085
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
143
Number
3
Pages
687-97.e1-9
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
BACKGROUND & AIMS: Gastrointestinal development requires regulated differentiation of visceral smooth muscle cells (SMCs) and their contractile activities; alterations in these processes might lead to gastrointestinal neuromuscular disorders. Gastrointestinal SMC development and remodeling involves post-transcriptional modification of messenger RNA. We investigated the function of the RNA-binding protein for multiple splicing 2 (RBPMS2) during normal development of visceral smooth muscle in chicken and expression of its transcript in human pathophysiological conditions.
METHODS: We used avian replication-competent retroviral misexpression approaches to analyze the function of RBPMS2 in vivo and in primary cultures of chicken SMCs. We analyzed levels of RBPMS2 transcripts in colon samples from pediatric patients with Hirschsprung's disease and patients with chronic pseudo obstruction syndrome (CIPO) with megacystis.
RESULTS: RBPMS2 was expressed strongly during the early stage of visceral SMC development and quickly down-regulated in differentiated and mature SMCs. Misexpression of RBPMS2 in differentiated visceral SMCs induced their dedifferentiation and reduced their contractility by up-regulating expression of Noggin, which reduced activity of bone morphogenetic protein. Visceral smooth muscles from pediatric patients with CIPO expressed high levels of RBPMS2 transcripts, compared with smooth muscle from patients without this disorder.
CONCLUSIONS: Expression of RBPMS2 is present in visceral SMC precursors. Sustained expression of RBPMS2 inhibits the expression of markers of SMC differentiation by inhibiting bone morphogenetic protein activity, and stimulates SMC proliferation. RBPMS2 transcripts are up-regulated in patients with CIPO; alterations in RBPMS2 function might be involved in digestive motility disorders, particularly those characterized by the presence of muscular lesions (visceral myopathies).
Keywords
Animals, Bone Morphogenetic Proteins/genetics, Bone Morphogenetic Proteins/metabolism, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cell Differentiation, Cell Proliferation, Cells, Cultured, Chick Embryo, Colon/metabolism, Colon/physiopathology, Colonic Pseudo-Obstruction/genetics, Colonic Pseudo-Obstruction/metabolism, Gastrointestinal Motility, Gene Expression Regulation, Developmental, Gizzard/embryology, Gizzard/metabolism, Hirschsprung Disease/genetics, Hirschsprung Disease/metabolism, Humans, Infant, Muscle Contraction, Muscle, Smooth/embryology, Muscle, Smooth/metabolism, Myocytes, Smooth Muscle/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, Time Factors, Transcription, Genetic, Transfection
Pubmed
Web of science
Create date
07/06/2013 10:48
Last modification date
20/08/2019 12:41
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