Cécile Notarnicola1, Caroline Rouleau2, Ludovic Le Guen1, Anne Virsolvy1, Sylvain Richard1, Sandrine Faure1, Pascal De Santa Barbara3. 1. INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier, France. 2. INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier, France; CHRU Montpellier, Service d'Anatomie Pathologique, Montpellier, France. 3. INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier, France. Electronic address: pascal.de-santa-barbara@inserm.fr.
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).
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).
Authors: Tyler R Huycke; Bess M Miller; Hasreet K Gill; Nandan L Nerurkar; David Sprinzak; L Mahadevan; Clifford J Tabin Journal: Cell Date: 2019-09-19 Impact factor: 41.582
Authors: Philippe Chetaille; Christoph Preuss; Silja Burkhard; Jean-Marc Côté; Christine Houde; Julie Castilloux; Jessica Piché; Natacha Gosset; Séverine Leclerc; Florian Wünnemann; Maryse Thibeault; Carmen Gagnon; Antonella Galli; Elizabeth Tuck; Gilles R Hickson; Nour El Amine; Ines Boufaied; Emmanuelle Lemyre; Pascal de Santa Barbara; Sandrine Faure; Anders Jonzon; Michel Cameron; Harry C Dietz; Elena Gallo-McFarlane; D Woodrow Benson; Claudia Moreau; Damian Labuda; Shing H Zhan; Yaoqing Shen; Michèle Jomphe; Steven J M Jones; Jeroen Bakkers; Gregor Andelfinger Journal: Nat Genet Date: 2014-10-05 Impact factor: 38.330
Authors: Thalia A Farazi; Carl S Leonhardt; Neelanjan Mukherjee; Aleksandra Mihailovic; Song Li; Klaas E A Max; Cindy Meyer; Masashi Yamaji; Pavol Cekan; Nicholas C Jacobs; Stefanie Gerstberger; Claudia Bognanni; Erik Larsson; Uwe Ohler; Thomas Tuschl Journal: RNA Date: 2014-05-23 Impact factor: 4.942