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

World J Gastroenterol. 2006 Feb 28;12(8):1211-8. doi: 10.3748/wjg.v12.i8.1211.

Abstract

Aim: To evaluate the possible differences in morphology and immunohistochemical expression of CD3, transforming growth factor beta1 (TGF-beta1), Smad7, alpha-smooth muscle actin (alpha-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-beta1 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-beta1 and Smad7 staining in the small and large intestine mucosa of Smad3 null mice as compared to wild-type mice. Alpha-Sma and collagen I-VII staining of small and large intestine did not differ between the two groups of mice. TGF-beta1 levels of colonic tissue homogenates were significantly higher in null mice than in wild-type mice. In preliminary experiments a significant reduction of TNBS-induced intestinal fibrosis was observed in null mice as compared to wild-type mice.

Conclusion: Smad3 null mice are a useful model to investigate the in vivo role of the TGF-beta/Smad signalling pathway in intestinal inflammation and fibrosis.

Publication types

  • Comparative Study

MeSH terms

  • Actins / analysis
  • Animals
  • CD3 Complex / analysis
  • Collagen / analysis
  • DNA / analysis
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrosis / pathology
  • Fibrosis / physiopathology
  • Immunity, Innate / genetics
  • Immunity, Innate / physiology
  • Immunohistochemistry
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology
  • Intestine, Large / chemistry*
  • Intestine, Large / pathology*
  • Intestine, Large / physiology
  • Intestine, Small / chemistry*
  • Intestine, Small / pathology*
  • Intestine, Small / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Smooth / chemistry
  • Phenotype
  • Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Smad3 Protein / genetics*
  • Smad3 Protein / physiology
  • Smad7 Protein / analysis
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / physiology
  • Transforming Growth Factor beta1

Substances

  • Actins
  • CD3 Complex
  • Smad3 Protein
  • Smad3 protein, mouse
  • Smad7 Protein
  • Smad7 protein, mouse
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Collagen
  • DNA