Regulation of corneal fibroblast MMP-1 secretion by cytochalasins.
Cytochalasins B (CB), dihydroB (H2CB), and D (CD) were found to cause loss of fibronectin (Fn) from the cell surface of normal rabbit corneal fibroblasts, breakdown of F-actin-containing microfilament bundles ("stress fibers"), and increase levels of type I interstitial collagenase (MMP-1) in the medium. In contrast to the effects of plasmin, the cytochalasins caused withdrawal of cells from the Fn mesh but not total loss of the mesh, and the collagenase was essentially all in latent form. The results are consistent with the possibility that cytochalasins, like plasmin, perturb the alpha 5 beta 1 integrin (Fn) receptor. Unlike plasmin, which degrades Fn to result in such a perturbation, however, the cytochalasins are thought to do so by directly disrupting cytoplasmic F-actin microfilaments associated with focal contact adhesive structures, to result in changes in the Fn receptor that cause loss of Fn. Thus, plasmin acting extracellularly and cytochalasins acting intracellularly are both thought to be able to modulate the secretion (and possibly also the synthesis) of MMP-1 by corneal fibroblasts by perturbing the Fn receptor located in the focal contact. The presence of all active collagenase after treatment with plasmin, as opposed to latent collagenase after treatment with cytochalasin, supports the interpretation that the events of secretion and activation of collagenase can be uncoupled.
Berman
M B
MB
Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas.
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D003319:Corneal Stroma / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003572:Cytochalasins / Q000494:pharmacology*; D005341:Fibrinolysin / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020781:Matrix Metalloproteinase 1; D011817:Rabbits; D017469:Receptors, Fibronectin / Q000378:metabolism
D000199:Actins; D003572:Cytochalasins; D005353:Fibronectins; D017469:Receptors, Fibronectin; D005341:Fibrinolysin; D017364:Collagenases; D020781:Matrix Metalloproteinase 1