Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) as a novel regulator of myogenic cell differentiation.
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.
Attia
Mohamed
M
Laboratoire CRRET, CNRS EAC 7149, Université Paris-Est Créteil, Créteil, France.
Mohamed
Attia
A
Huet
Eric
E
Eric
Huet
H
Delbé
Jean
J
Jean
Delbé
D
Ledoux
Dominique
D
Dominique
Ledoux
L
Menashi
Suzanne
S
Suzanne
Menashi
M
Martelly
Isabelle
I
Isabelle
Martelly
M
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
D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D051926:Basigin; D020782:Matrix Metalloproteinases