NOV/CCN3 induces adhesion of muscle skeletal cells and cooperates with FGF2 and IGF-1 to promote proliferation and survival.
During mammalian development, expression of the Nephroblastoma overexpressed gene (NOV/CCN3) is tightly regulated in skeletal muscles. Ex vivo, ectopic expression of NOV blocks myogenic differentiation. NOV also supports endothelial cell adhesion and angiogenesis through interactions with integrins. Integrins play fundamental roles during myogenesis. In this study, we show that NOV mediates adhesion and spreading of myoblasts. Myoblasts adhesion to NOV does not require proteoglycans and is dependent on integrin beta1, whereas spreading involves another RGD-sensitive integrin. The C-Terminal part of NOV as well as full-length is able to support adhesion of myoblasts; in addition, both increase focal-adhesion kinase (FAK) phosphorylation. Furthermore, NOV is an adhesive substrate that, combined with FGF2 or IGF-1, promotes cell specific proliferation and survival, respectively, in a better way than fibronectin. Taken together, these results identify NOV as an adhesion substrate for myoblasts which, in concert with growth factors, could play a role in the physiology of muscle cells.
Lafont
Jerôme
J
Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
Thibout
Hélène
H
Dubois
Catherine
C
Laurent
Maryvonne
M
Martinerie
Cécile
C
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology; D055514:Nephroblastoma Overexpressed Protein; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C526319:CCN3 protein, human; C526320:Ccn3 protein, mouse; D017874:Immediate-Early Proteins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D011509:Proteoglycans; D016222:Fibroblast Growth Factor 2; D055513:Connective Tissue Growth Factor; D007334:Insulin-Like Growth Factor I; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases