Smad3 knock-out mice as a useful model to study intestinal fibrogenesis

AIM： To evaluate the possible differences in morphology and immunohistochemical expression of CD3, transforming growth factor 131（TGF-131）, Smad7, α-smooth muscle actin （α-Sma）, and collagen types Ⅰ-Ⅶ of small and large intestine in Smad3 null and wild-type mice. METHODS： Ten null and ten wild-type adult mice were sacrificed at 4 mo of age and the organs （esophagus, small and large bowel, ureters） were collected for histology（hematoxylin and eosin, Masson thrichrome, silver staining）, morphometry and immunohistochemistry analysis. TGF-β1 levels of intestinal tissue homogenates were assessed by ELISA. RESULTS： No macroscopic intestinal lesions were detected both in null and wild-type mice. Histological and morphometric evaluation revealed a significant reduction in muscle layer thickness of small and large intestine in null mice as compared to wild-type mice. Immunohistochemistry evaluation showed a significant increase of CD3＋T cell, TGF-β1 and Smad7 staining in the small and large intestine mucosa of Smad3 null mice as compared to wild-type mice. α-Sma and collagen Ⅰ-Ⅶ staining of small and large intestine did not differ between the two groups of mice. TGF-β1 levels of colonic tissue homogenates were significantly higher in null mice than in wildtype mice. In preliminary experiments a significant reduction of TNBS-induced intestinal fibrosis was observed in null mice as compared to wild-type mice.