TGF-β1 mediates the regulation of the expression of MMP-2 in cultured rat mesangial cell

Purpose: To study the regulatory effect of all-trans retinoic acid (ATRA) on the cultured rat mesangial cell expressing MMP-2 and the possible relationship between the transforming growth factor-β1 and the regulation of ATRA on the MMP-2 expression. Methods: The Northern blot, Western blot and Zymography assays were used to detect the expression of the mRNA, protein and zymatic activity of MMP-2 of cultured mesangial cell and the TGF-β1 transfectants. Results: ATRA upregulated the expression of MMP-2 mRNA and secretion of MMP-2 proteins, and increased enzymatic activity of MMP-2 in cultured mesangial cell. Besides, ATRA also increased a dose-dependent increase in the secretion of transforming growth factor-β1 (TGF-β1) peptides. Antisense TGF-β1 construct almost completely blocked secretion of active TGF-β1 peptides in the antisense- bearing transfectants. Northern blot analysis showed that the transfectants treated with 10^-6 mol/L ATRA for 72 h neither increased nor decreased the levels of MMP-2 mRNA. Moreover, addition of anti-TGF-β1 antibodies to mesangial cell in the presence of 10-6 mol/L ATRA reduced ATRA-induced MMP-2 expression dose dependently. Conclusions: ATRA upregulated the expression of MMP-2 mRNA. ATRA also increased the secretion of MMP-2 protein and the enzymatic activity. TGF-β1 regulated the expression of MMP-2 in mesangial cell and it is necessary for the regulatory effect of ATRA. These data suggest that TGF-β1 might be involved in ATRA-induced MMP-2 expression.