Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodelling cornea.
We have documented changes in collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in remodelling rabbit cornea. MMP-2 (65 kDa gelatinase) in the proenzyme form is synthesized by the cells of the normal corneal stroma. After keratectomy the level of MMP-2 is increased in the stroma and enzyme appears in both pro- and activated forms. In addition, corneal cells synthesize MMP-9 (92 kDa gelatinase) in the proenzyme form after keratectomy; expression occurs in both the epithelial as well as stromal corneal layers. Changes in expression of both enzymes are precisely localized to the repairing portion of cornea, but demonstrate important differences in timing that correlate with the timing of specific events of matrix remodelling. Our data suggest that each of the gelatinases plays a different role in tissue remodelling after injury. We hypothesize that MMP-2 performs a surveillance function in normal cornea, catalyzing degradation of collagen molecules that occasionally become damaged. After wounding, this enzyme appears to participate in the prolonged process of collagen remodelling in the corneal stroma that eventually results in functional regeneration of the tissue. MMP-9 expression does not correlate with stromal remodelling, but we suggest that the enzyme might play a part in controlling resynthesis of the epithelial basement membrane.
Matsubara
M
M
Eye Research Institute, Boston, Massachusetts.
Girard
M T
MT
Kublin
C L
CL
Cintron
C
C
Fini
M E
ME
D000818:Animals; D015153:Blotting, Western; D002846:Chromatography, Affinity; D003315:Cornea / Q000201:enzymology*; D005109:Extracellular Matrix / Q000201:enzymology*; D005131:Eye Injuries / Q000378:metabolism; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000502:physiology*; D003012:Microbial Collagenase / Q000096:biosynthesis; D011817:Rabbits; D014945:Wound Healing / Q000502:physiology*
D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D003012:Microbial Collagenase