Details

Autor(en) / Beteiligte

• Huet, Clotilde
• Li, Zhi-Fang
• Liu, Hai-Zhen
• Black, Roy A
• Galliano, Marie-Florence
• Engvall, Eva

Titel

Skeletal muscle cell hypertrophy induced by inhibitors of metalloproteases; myostatin as a potential mediator

Ist Teil von

• American Journal of Physiology: Cell Physiology, 2001-11, Vol.281 (5), p.C1624-C1634

Ort / Verlag

United States

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 1  The Burnham Institute, La Jolla, California 92037; 2  Institut National de la Santé et de la Recherche Médicale-Institut National de la Recherche Agronomique U418, Communications Cellulaires et Différenciation, Hôpital Debrousse, 69322 Lyon, France; 3  Research Administration, Immunex Corporation, Seattle, Washington 98101; and 4  Centre National de la Recherche Scientifique UPR 2163, Physiologie Moléculaire et Cellulaire, Centre Hospitalier Universitaire Purpan, 31059 Toulouse Cedex 03, France Cell growth and differentiation are controlled in many tissues by paracrine factors, which often require proteolytic processing for activation. Metalloproteases of the metzincin family, such as matrix metalloproteases and ADAMs, recently have been shown to be involved in the shedding of growth factors, cytokines, and receptors. In the present study, we show that hydroxamate-based inhibitors of metalloproteases (HIMPs), such as TAPI and BB-3103, increase the fusion of C 2 C 12 myoblasts and provoke myotube hypertrophy. HIMPs did not seem to effect hypertrophy via proteins that have previously been shown to regulate muscle growth in vitro, such as insulin-like growth factor-I, calcineurin, and tumor necrosis factor- . Instead, the proteolytic maturation of myostatin (growth differentiation factor-8) seemed to be reduced in C 2 C 12 cells treated with HIMPs, as suggested by the presence of nonprocessed myostatin precursor only in hypertrophic myotubes. Myostatin is a known negative regulator of skeletal muscle growth, belonging to the transforming growth factor- /bone morphogenetic protein superfamily. These results indicate that metalloproteases are involved in the regulation of skeletal muscle growth and differentiation, that the proteolytic maturation of myostatin in C 2 C 12 cells may be directly or indirectly linked to the activity of some unidentified HIMP-sensitive metalloproteases, and that the lack of myostatin processing on HIMP treatment may be a mediator of myotube hypertrophy in this in vitro model. metalloendopeptidases; protease inhibitor; growth and differentiation factor-8