title: Endothelin induces functional hypertrophy of peritubular smooth muscle cells.
abstract: When chronically stimulated with agonists of contraction, smooth muscle cells (SMCs) undergo cell hypertrophy, a process defined as increase in size and potentiation of the contractile phenotype in the absence of proliferation. Hypertrophic response has long been associated to a number of pathologies of the cardiovascular and respiratory systems. We have investigated the phenotypic and functional response of SMCs to long-term treatment with endothelin. Our model was primary cultures of peritubular smooth muscle cells (PSMC) a testicular cell type target of locally produced endothelin and characterized by an unusual phenotypic stability when cultured in simple medium in complete absence of serum. We report the following responses of PSMC to 4-day exposure to ET-1: (i) increased protein synthesis without induction of cell proliferation; (ii) increase in cell size (evaluated by means of flow cytometry) and increased expression of SM-alpha-actin, desmin, caldesmon and calponin, markers of the contractile phenotype. In experiments of selective stimulation of either ETA or ETB receptor subtypes, both proved to be involved in inducing the observed hypertrophic responses. The hypertrophic cells exhibit the ultrastructural features of differentiated SMCs and are capable of calcium mediated contractile response when acutely stimulated with ET-1 specifically through ETA and/or ETB receptors, as evaluated by calcium imaging and scanning electron microscopy. These observations demonstrate that engagement of ET receptors is capable of inducing potentiation of the contractile phenotype and functional hypertrophy of PSMC.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Histology and Medical Embryology, "La Sapienza" University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Romano
authors.forename: Guido
authors.initials: G
authors.lastname: Gambara
authors.forename: Paola
authors.initials: P
authors.lastname: De Cesaris
authors.forename: Elio
authors.initials: E
authors.lastname: Ziparo
authors.forename: Fioretta
authors.initials: F
authors.lastname: Palombi
authors.forename: Antonio
authors.initials: A
authors.lastname: Filippini
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D006984:Hypertrophy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012671:Seminiferous Tubules / Q000166:cytology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016232:Endothelins