Regulation of Corneal Fibroblast MMP-1 Collagenase Secretion by Plasmin

Plasmin was found to degrade the fibronectin (Fn) mesh produced by cultures of normal rabbit corneal fibroblasts, cause breakdown of F-actin-containing microfilament bundles (“stress fibers”), and increase levels of active type I interstitial collagenase (MMP-1) in the medium. Fibroblast cultures derived from alkali-burned, ulcerating rabbit corneas also responded to plasmin by secreting collagenase, detected only in active form. Moreover, harvests from organ cultures of ulcerating corneas not only had higher levels of urokinase-like plasminogen activator (uPA) than normal cultures but also had higher levels of Fn degradation fragments. The results are consistent with reports that indicate that perturbation of the α5β1, integrin (Fn) receptor by proteolytic fragments of Fn causes the increased synthesis and secretion of MMP-1. The uPA/ plasmin system, therefore, might have an important role in regulating collagenase synthesis, secretion, and activation during wound remodelling and stromal ulceration.