title: Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) as a novel regulator of myogenic cell differentiation.
abstract: Matrix metalloproteinases (MMPs) are thought to play an important role in skeletal muscle cell growth and differentiation. In view of the MMP inducing function of EMMPRIN/CD147, its role in myogenic cell differentiation was investigated. EMMPRIN level increased during differentiation of both rat primary myoblasts derived from satellite cells and mouse C2.7 myogenic cells and was associated with an alteration in its molecular forms. In parallel, expression of pro-MMP-9 gradually decreased and that of pro-MMP-2 and active MMP-2 increased. While small interfering RNA (siRNA) inhibition of EMMPRIN expression accelerated cell differentiation, exogenously added recombinant EMMPRIN inhibited differentiation by an MMP-mediated mechanism, as the MMP inhibitor marimastat abrogated EMMPRIN's effect. Our results further suggest that EMMPRIN regulates differentiation through an MMP activation of transforming growth factor beta (TGFβ), a known inhibitor of myoblast's differentiation, as the increased activation and signaling of TGFβ by EMMPRIN was attenuated in the presence of marimastat. EMMPRIN inhibition may thus represent a novel strategy in the treatment of muscular degenerative disorders.
authors.affiliation: Laboratoire CRRET, CNRS EAC 7149, Université Paris-Est Créteil, Créteil, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Attia
authors.forename: Attia
authors.initials: A
authors.lastname: Mohamed
authors.forename: Eric
authors.initials: E
authors.lastname: Huet
authors.forename: Huet
authors.initials: H
authors.lastname: Eric
authors.forename: Jean
authors.initials: J
authors.lastname: Delbé
authors.forename: Delbé
authors.initials: D
authors.lastname: Jean
authors.forename: Dominique
authors.initials: D
authors.lastname: Ledoux
authors.forename: Ledoux
authors.initials: L
authors.lastname: Dominique
authors.forename: Suzanne
authors.initials: S
authors.lastname: Menashi
authors.forename: Menashi
authors.initials: M
authors.lastname: Suzanne
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martelly
authors.forename: Martelly
authors.initials: M
authors.lastname: Isabelle
mesh_terms: D000818:Animals; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000201:enzymology / Q000502:physiology; D020868:Gene Silencing; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D051926:Basigin; D020782:Matrix Metalloproteinases