Modulation of matrix metalloproteinase and TIMP-1 expression by TGF-beta1 in cultured human RPE cells.
In order to investigate the effects of TGF-beta1 on the expression of MMP-2, -9 and TIMP-1 in human retinal pigment epithelial (RPE) cells, the third-sixth passage cultured RPE cells were treated with TGF-beta1 at different concentrations (0.01, 0.1, 1.0, 10 ng/mL), the expression of MMP-2, -9 and TIMP-1 mRNA was detected by semi-quantitative RT-PCR assays. MMP-2, -9 and TIMP-1 mRNA were expressed in the cultured RPE cells. The values of MMP-2/beta-actin in the cells treated with 0.1, 1.0, 10 ng/mL TGF-beta1 were 1.04 +/- 0.04, 1.07 +/- 0.02 and 1.11 +/- 0.03, respectively, significantly higher than in the control group (0.96 +/- 0.03, P < 0.05-0.01). The expression of MMP-2 mRNA could be up-regulated by TGF-beta1, in a dose-dependent manner. The expression of MMP-9 mRNA in the cultured RPE cells was slightly up-regulated by various TGF-beta1 concentrations treatment. The values of TIMP-1/beta-actin in the cells treated with 0.01 and 0.1 ng/ mL TGF-beta1 were 0.85 +/- 0.01 and 0.97 +/- 0.02 respectively, significantly lower than in the control group (1.07 +/- 0.04, P < 0.01), indicating that the expression of TIMP-1 mRNA was down-regulated by TGF-beta1 at low concentrations. But along with the increase of TGF-beta1 concentrations (1.0 and 10 ng/mL), the expression of TIMP-1 mRNA was slightly up-regulated, not significantly different from that in the control group (P > 0.05). It was concluded that TGF-beta1 might play an important role in the up-regulation of the expression of MMP-2 in RPE cells and result in a directional shift in the balance between MMP and TIMP. This may be facilitated for RPE cells to migrate in the pathogenesis of vitreoretinopathy.
Zeng
Aiping
A
Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zeng
Shuiqing
S
Cheng
Yang
Y
Xiao
Qing
Q
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9