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ABSTRACT: SMAD3 is one of the receptor-activated SMADs which are important in TGF-beta signal transduction. Smad3-null mice show accelerated cutaneous wound healing compared with wild-type mice. In this work, we investigated the functions and the mechanism of Smad3-mediated TGF-beta signal on matrix metaloproteinase-2 (MMP-2) in mouse fibroblast. We found that MMP-2 at wound bed was expressed earlier in Smad3-null mice than that in wild type and heterozygotes. In the sera of wounding mice, the activity of MMP-2 was also remarkably higher in Smad3-null mice than that in the other two. The embryonic fibroblasts were separated from Smad3 knockout mice to test the function of Smad3 in modulating the expression of MMP-2. The results showed that the expression and activity of MMP-2 in Smad3-null fibroblasts were higher than those in wild type cells. TGF-beta1 could increase the MMP-2 activities in both Smad3 mutant and wild type fibroblasts. The expression and activity of MMP-2 were inhibited by over expression of SMAD3 in Smad3-null fibroblasts, while the expression and activity of MMP-2 were increased by over expression of anti-sense Smad3 in wild type cells. All these results showed that SMAD3 inhibited the expression of MMP-2 in mouse embryonic fibroblasts.
Acta Genetica Sinica 07/2005; 32(6):633-40.