Coordinate expression of matrix-degrading proteinases and their activatorsand inhibitors in bovine skeletal muscle

Matrix metalloproteinases (MMP) responsible for degradation of connective t issue are found in most tissues. The MMP are regulated at the levels of tra nscription, zymogen activation by plasmin or membrane-type- (MT) MIMP, and control of enzyme activity by tissue inhibitors of metalloproteinases (TIMP ). Whole bovine skeletal muscle showed multiple MMP activities on gelatin z ymography and also expressed mRNA encoding MMP-1, -2, -9, -14, and -16, tis sue inhibitors of metalloproteinase (TIMP)-1, -2, and -3 and plasminogen ac tivator and its receptor. Purified intramuscular fibroblasts and myogenic c ell culture derived from satellite cells expressed most or all of these ele ments. Statistical analysis (n = 35) revealed a strong positive correlation among the mRNA levels of several elements of the MMP system, including MMP -8, MMP-14, TIMP-1, -2, and -3 (r = 0.014 to 0.930, P < 0.0001). Our result s provide an extensive profile of an extracellular proteolytic cascade invo lving MMP in skeletal muscle and suggest that 1) the activation cascades of muscle MMP may be initiated by both plasmin and membrane-type MMP; 2) a gr oup of genes involved in the same "arm" of zymogen activation are coexpress ed in this tissue; and 3) skeletal muscle cells, in addition to the intramu scular fibroblasts, express an extensive complement of MMP and related prot eins.