Protease nexin I, a serpin, inhibits plasminogen-dependent degradation of muscle extracellular matrix

✍ Scribed by J. S. Rao; Dr. Mrs. C. B. Kahler; Dr. J. B. Baker; Dr. B. W. Festoff

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 663 KB
• Volume: 12
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/mus.880120805

✦ Synopsis

Clonal, fusing, mouse skeletal muscle cells (C2) were grown to the myotube stage (90% confluence) before they were subjected to isotopecontaining serum-free media (3H-proline or 35S-methionine). C2 myotubes secrete and organize a biosynthetically labeled matrix which adheres to the plastic after removal of myotubes with detergent and ammonium hydroxide. When these homotypic-labeled myotube matrices were incubated with myoblast-conditioned media containing high specific activity urokinase-type plasminogen activator, slow, but clearly detectable, release of label occurred. However, degradation of matrix, with solubilization of label, was accelerated sixfold by addition of human plasminogen to diluted myoblastconditioned media. If protease nexin I, a cellular serine protease inhibitor purified from human fibroblast-conditioned media, was added (0.2 pg/ml) with plasminogen, inhibition of matrix hydrolysis by 52% occurred. Higher concentrations (0.8 pgiml or above) of protease nexin I completely inhibited the degradation of extracellular matrix components. A similar protease inhibitor was purified from C2 myotube-conditioned media, and this molecule also inhibited the plasminogen-dependent release of extracellular matrix. We propose that protease nexin I inhibits the destruction of myotube matrix by inactivating the plasmin/plasminogen activation system and may be the physiologic regulator of this system during muscle development in vivo. Key words: murine 0 plasminogen activators 0 serine proteases regeneration trophic