UNIQUE REGULATION OF THE MATRIX METALLOPROTEINASE, GELATINASE-B

Purpose. The matrix metalloproteinase (MMP), gelatinase B, is expresse d by both corneal cell types found at the epithelial-stromal tissue in terface, the site of basement membrane repair in the healing cornea. T his study investigates the relative regulation of gelatinase B compare d to other MMPs in response to agents related to those found in the co rneal repair environment or in corneal ulcers. Methods. A culture mode l of corneal cells isolated from rabbit was used. Results. Gelatinase B is the major MMP expressed by corneal epithelial cells, whereas stro mal fibroblasts produce gelatinase B along with three other MMPs: coll agenase, stromelysin, and gelatinase A. Phorbol-12-myristate 13-acetat e (PMA) stimulates gelatinase B mRNA. and protein synthesis by corneal cells, which is similar to its effect on the other MMPs. Stimulation occurs, at least partially, at the transcriptional level. PMA-stimulat ed MMP expression follows biphasic kinetics, with the major effect on collagenase, stromelysin, and gelatinase A occurring during the late c omponent. In contrast, the major gelatinase B response occurs during t he early component. Transforming growth factor-beta (TGF-beta) has no effect on constitutive expression of gelatinase B by fibroblasts; howe ver, expression stimulated by PMA is enhanced. In contrast, constituti ve expression of collagenase and stromelysin is inhibited by TGF-beta. However, in the presence of PMA, the initial inhibitory effect of TGF -beta is reversed after treatment. Conclusion. Gelatinase B expression is regulated differently from other corneal MMPs. This provides a mec hanism for control of basement membrane repair independent of repair p rocesses in the stroma.