STROMAL FIBROBLASTS SYNTHESIZE COLLAGENASE AND STROMELYSIN DURING LONG-TERM TISSUE REMODELING

The process of connective tissue remodeling is an important mechanism contributing to tissue morphogenesis in development and homeostasis. A lthough it has long been known that remodeling tissues actively mediat e collagenolysis, little is understood about the molecular mechanisms controlling this cell-regulated process. In this study, we examined th e biosynthesis of collagenase and the related metalloproteinase, strom elysin, during remodeling of repair tissue deposited after mechanical injury to the rabbit cornea. Neither enzyme was synthesized by uninjur ed corneas; however, synthesis and secretion was detectable within one day after injury. Collagenase accumulated in its latent form while st romelysin appeared to be partially activated. Enzymes were synthesized by cells having a fibroblast phenotype. These cells were found within the stroma. New synthesis was correlated with accumulation of enzyme- specific mRNA. Highest levels of enzyme synthesis were observed in the repair tissue. However, stromal cells outside of the repairing area a lso synthesized both enzymes. The level of synthesis decreased in a gr adient radiating from the repair tissue. Total synthetic levels in a g iven area of cornea were dependent on both the number of cells express ing enzyme and the rate of enzyme synthesis. Synthesis of collagenase was detected in repair tissue as long as nine months after injury. Our findings provide direct support for the hypothesis that new collagena se synthesis by cells in repair tissue is the first step in collagen d egradation during long-term tissue remodeling.