1. Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo‐obstruction syndrome
- Author
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Annick Bourret, Delphine Martire, Christophe Chardot, John Rendu, Marc Bellaiche, Sarah Garnier, Dominique Berrebi, Pascal de Santa Barbara, Sébastien Sagnol, Sandrine Faure, Stéphane Marchal, Nicolas Kalfa, D. Forgues, Amandine Guérin, Norbert Chauvet, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Intestinal pseudo-obstruction ,Male ,Adolescent ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Myocytes, Smooth Muscle ,chronic intestinal pseudo‐obstruction Disease ,PDGFR pathway ,PDGFRA ,Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Myocyte ,Humans ,Progenitor cell ,Child ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,Cell Proliferation ,Phenotypic plasticity ,Growth factor ,Mesenchymal stem cell ,Intestinal Pseudo-Obstruction ,Cell Differentiation ,Cell Biology ,Original Articles ,medicine.disease ,musculoskeletal system ,Phenotype ,Cell biology ,smooth muscle cells ,030104 developmental biology ,030220 oncology & carcinogenesis ,plasticity ,cardiovascular system ,Molecular Medicine ,Original Article ,Female ,tissues ,intestinal motility disorders ,Muscle Contraction ,Signal Transduction - Abstract
Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo‐obstruction (CIPO) syndrome, a life‐threatening intestinal motility disorder. We showed that CIPO‐SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet‐Derived Growth Factor Receptor‐alpha (PDGFRA) expression. We showed that this modulation occurs without origin‐related differences in CIPO circular and longitudinal‐derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO‐SMC towards an undifferentiated stage. The development of CIPO‐SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO.
- Published
- 2021
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