Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

Abstract

Transforming growth factor-β (TGF-β) 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-β1 on the gene expression of matrix metalloproteinase-2 (MMP-2) in lens epithelial cells (LECs). The results showed that TGF-β1 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 α-smooth muscle actin. We also showed that an MMP inhibitor blocked the TGF-β1-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.

TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity

“…*P Ͻ 0.05. C: transduction of recombinant PRDX6 protein in LECs isolated from SCR rat lens ( LECs from these rats contain elevated levels of ROS and bioactive TGF-␤1 with overmodulation of TGF-␤1-inducible genes such as ␣-sm actin and ␤ig-h3, and these genes are implicated in the pathophysiology of cataractogenesis (6,18,40,60). Furthermore, we found that ROS-driven oxidative stress could also influence downstream signaling in SCR ϩ LECs, such as attenuation of transcriptional activity of LEDGF.…”

Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury

“…MMP-2 has been associated with EMT in other cellular systems. Seomun et al (30) demonstrated that MMP-2 mediated TGF-␤1-dependent EMT of cultured lens epithelial cells, resulting in the generation of a myofibroblast-like phenotype. Song et al (31) examined the role of MMP-2 in the epithelial-mesenchymal transition of cardiac endocardial cushions.…”

Direct contribution of epithelium to organ fibrosis: epithelial-mesenchymal transition

“…In vitro and in vivo studies have shown that injurytriggered TGFβ/Smad/Snail signaling is responsible for this transition [63]. TGFβ induces MMP expression, and inhibition of MMP activity prevents TGFβ-induced EMT, suggesting that the degradation of extracellular matrix components is a critical signal for TGFβ-triggered EMT of lens epithelial cells [64].…”