Résumé :
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The plasticity of Smooth Muscle Cells (SMCs) is a hallmark of these muscular type. Under exogenous stimulation, SMCs trigger their dedifferentiation and conduct to their proliferation. Bone Morphogenetic Protein (BMP) pathway was shown to control the induction of contractile phenotype of vascular SMCs and its inhibition is associated with the remodeling process.The gastrointestinal musculature is a complex structure compound of visceral SMCs, and associated cells such enteric neural crest-derived cells and Interstitial Cells of Cajal (ICCs). Visceral SMCs derive from the visceral mesenchymal precursor cells and differentiate during the embryonic period to produce functional and contractile cells. The visceral SMCs have similar features with the others SMCs such as remodeling process in diverse pathologies. In addition, we showed that visceral SMC differentiation process is regulated by BMP pathway. Post-transcriptional events regulate the final fate of mRNAs and determine their spatiotemporal pattern of expression. Ribonucleoprotein complexes control multiples steps of this process including mRNA cellular localization, splicing, translational inhibition and activation or mRNA degradation. These complexes contain specific RNA-binding proteins (RBP) that play important role in gene regulation during the development. One large family of RBP is characterized by RNA Recognition Motifs (RRMs). These proteins are involved in RNA metabolism and are expressed in a tissue-specific manner, suggesting that RBPs may be involved in developmental processes and pattern formation. Previous studies identified Rbpms2 (RBP for Multiple Splicing 2 that contains one RRM domain) expression in embryonic heart and gastrointestinal tract.Here we report the function and mechanism of action of the RNA-binding protein Rbpms2 during visceral SMC development, phenotypic plasticity and its expression in human GI motility disorders. We show that Rbpms2 is an early marker of visceral SMC precursors and that ectopic expression of Rbpms2 in mature SMCs increases their proliferation, and alters their contractile differentiation. The contractile differentiation defect induced by Rbpms2 is mediated by its capacity to inhibit BMP signaling through the positive control of the expression of its major inhibitor, Noggin. In summary, we show that ectopic Rbpms2 expression in our in vivo and cellular models could phenocopy the alteration of the contractile function observed in human visceral myopathy.
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