Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo‐obstruction syndrome. Issue 8 (3rd March 2021)

• Record Type: Journal Article
• Authors: Martire, Delphine; Garnier, Sarah; Sagnol, Sébastien; Bourret, Annick; Marchal, Stéphane; Chauvet, Norbert; Guérin, Amandine; Forgues, Dominique; Berrebi, Dominique; Chardot, Christophe; Bellaiche, Marc; Rendu, John; Kalfa, Nicolas; Faure, Sandrine; de Santa Barbara, Pascal
• Is Part Of: Journal of cellular and molecular medicine. Volume 25:Issue 8(2021)
• Page Start: 4028
• Page End: 4039
• Publication Date: 2021-03-03
• Subjects: chronic intestinal pseudo‐obstruction Disease -- intestinal motility disorders -- PDGFR pathway -- plasticity -- smooth muscle cells; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.16367
• Languages: English
• ISSNs: 1582-1838

Abstract

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.