BISINDOLYLMALEIMIDE INHIBITS THE PMA-INDUCED DOWN-REGULATION OF COLLAGEN-SYNTHESIS IN FIBROBLASTS

We assessed the role of protein kinase C (PKC) in the regulation of co llagen synthesis. Two PKC activators, Phorbol 12-myristate 13-acetate (PMA) and 1-oleyl 2-acetyl-sn-glycerol (GAG), decreased the relative r ate of collagen synthesis in a dose- and time-dependent manner in fibr oblasts, whereas an inactive phorbol ester, 4 alpha-phorbol didecanoat e failed to affect the collagen synthesis. In PKC-depleted cells both PMA and OAG were unable to inhibit collagen synthesis. Bisindolylmalei mide, a specific inhibitor of PKC, completely abrogated PMA-induced in hibition of collagen synthesis in a dose-dependent fashion while two O ther PKC inhibitors with low specificity, H7 and staurosporin failed t o block PMA effect on collagen synthesis. The results provide evidence that collagen synthesis is regulated through the signal pathway invol ving PKC activation.