[SMAD3 inhibits the expression of MMP-2 in mouse embryonic fibroblasts].
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.
Mao
Chun-Ming
CM
Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China.
Yang
Xiao
X
Lü
Ya-Xin
YX
Sun
Yan-Xun
YX
Cheng
Xuan
X
Huang
Cui-Fen
CF
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
D016373:DNA, Antisense; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2