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 alpha 5 beta 1 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.
Berman
M B
MB
Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas 75235-9057.
D000199:Actins / Q000378:metabolism; D000818:Animals; D002057:Burns, Chemical / Q000201:enzymology; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology; D003320:Corneal Ulcer / Q000201:enzymology; D005126:Eye Burns / Q000139:chemically induced / Q000201:enzymology; D005341:Fibrinolysin / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005353:Fibronectins / Q000378:metabolism; D020781:Matrix Metalloproteinase 1; D010958:Plasminogen / Q000494:pharmacology; D011817:Rabbits; D012972:Sodium Hydroxide; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology
D000199:Actins; D005353:Fibronectins; D012972:Sodium Hydroxide; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D020781:Matrix Metalloproteinase 1