Myodulin is a novel potential angiogenic factor in skeletal muscle.
We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in muscle fibers and cultured muscle cells. Myodulin RNA messengers were found in muscle fibers and their tendon extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein. Myodulin functions were assessed from similarities with chondromodulin-I. Coculture experiments using C(2)C(12) mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion. Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions. This role is consistent with the correlation between modulations in myodulin expression and modifications in muscle microvascularization associated with activity-dependent muscle mass variations.
Pisani
Didier F
DF
CNRS UMR 6548, Faculté des Sciences, Parc Valrose 06108 Nice cedex 2, France.
Pierson
Patricia M
PM
Massoudi
Ali
A
Leclerc
Lilian
L
Chopard
Angèle
A
Marini
Jean-François
JF
Dechesne
Claude A
CA
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002455:Cell Division; D002460:Cell Line; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D043925:Angiogenesis Inducing Agents; C489408:Cnmd protein, mouse; C489407:Cnmd protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C486027:Tnmd protein, rat