Unique regulation of the matrix metalloproteinase, gelatinase B.
OBJECTIVE
The matrix metalloproteinase (MMP), gelatinase B, is expressed by both corneal cell types found at the epithelial-stromal tissue interface, the site of basement membrane repair in the healing cornea. This study investigates the relative regulation of gelatinase B compared to other MMPs in response to agents related to those found in the corneal repair environment or in corneal ulcers.


METHODS
A culture model of corneal cells isolated from rabbit was used.


RESULTS
Gelatinase B is the major MMP expressed by corneal epithelial cells, whereas stromal fibroblasts produce gelatinase B along with three other MMPs: collagenase, stromelysin, and gelatinase A. Phorbol-12-myristate 13-acetate (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-stimulated MMP expression follows biphasic kinetics, with the major effect on collagenase, stromelysin, and gelatinase A occurring during the late component. In contrast, the major gelatinase B response occurs during the early component. Transforming growth factor-beta (TGF-beta) has no effect on constitutive expression of gelatinase B by fibroblasts; however, expression stimulated by PMA is enhanced. In contrast, constitutive 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.


CONCLUSIONS
Gelatinase B expression is regulated differently from other corneal MMPs. This provides a mechanism for control of basement membrane repair independent of repair processes in the stroma.
Fini
M E
ME
Massachusetts General Hospital, Cutaneous Biology Research Center, Charlestown 02129.
Girard
M T
MT
Matsubara
M
M
Bartlett
J D
JD
D000818:Animals; D001483:Base Sequence; D001485:Basement Membrane / Q000201:enzymology; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects / Q000201:enzymology*; D003319:Corneal Stroma / Q000201:enzymology; D017931:DNA Primers; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate