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

World Journal of Gastroenterology 2006年第8期12卷 1211-1218页

作者： Giuliana Zanninelli Antonella Vetuschi Roberta Sferra Angela D'Angelo amato fratticci Maria Adelaide Continenza Maria Chiaramonte Eugenio Gaudio Renzo Caprilli Giovanni Latella Cattedra di Gastroenterologia Università degli Studi di L'AquilaL'AquilaItaly Cattedra di Anatomia Umana Università degli Studi di L'AquilaL'AquilaItaly Dipartimento di Medicina Sperimentale Università degli Studi di L'AquilaL'AquilaItaly Università degli Studi di Roma"La Sapienza" Roma Italy Cattedra di Gastroenterologia I Università degli Studi di Roma"La Sapienza"RomaItaly

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.

关键词： Transforming growth factor TGF-13 Fibrosis Smad proteins

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