Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells.
Transforming growth factor-beta (TGF-beta) is known to be a causative factor in pathological fibrosis and the metastasis of cancer cells, through effects on molecules of the extracellular matrix (ECM). We evaluated the influence of TGF-beta(1) on the gene expression of matrix metalloproteinase-2 (MMP-2) in lens epithelial cells (LECs). The results showed that TGF-beta(1) induced the expression of mRNA for MMP-2 in LECs. Subsequently, in order to examine the role of MMP-2, we overexpressed MMP-2 in LECs by stable transfection. The MMP-2-overexpressing LECs showed typical indicators of a myofibroblast-like cell phenotype, such as multiple layers of cells, elongated morphology, and expression of alpha-smooth muscle actin. We also showed that an MMP inhibitor blocked the TGF-beta(1)-induced morphological change in LECs. These results demonstrate that MMP-2 plays a role in the transformation of LECs, which has implications for the pathological fibrosis of these cells.
Seomun
Y
Y
Laboratory of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea.
Kim
J
J
Lee
E H
EH
Joo
C K
CK
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000201:enzymology* / Q000648:ultrastructure; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000201:enzymology* / Q000648:ultrastructure; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D008854:Microscopy, Electron; D009924:Organ Culture Techniques; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D018076:DNA, Complementary; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2