Role and mechanism of tumor necrosis factor ligand-related molecule 1A in chronic experimental colitis associated intestinal fibrosis
Rongrong Zhan, Dong Wang, Wenxiu Jia, Jia Song, Mengyao Wu, Hui Li, Fengrong Yin, Na Wang, Chenxing Peng, Hong Zhang, Mei Song, Shuang Chen, David Quan Shih, Xiaolan Zhang
Abstract
ObjectiveTo explore the role and mechanism of tumor necrosis factor ligand-related molecule 1A (TL1A) in chronic experimental colitis associated intestinal fibrosis.
MethodsThe model of chronic experimental colitis-associated intestinal fibrosis was induced by dextran sodium sulfate (DSS). The mice with high TL1A (L-Tg) expression in lymphoid cells and wild-type mice with the same genetic background were divided into wild type control group, wild type DSS group, transgenic control group and transgenic DSS group. The changes of body mass, length of colon, disease activity index (DAI) and colonic pathological score were compared among different groups. The degree of colonic inflammation was evaluated by Hematoxylin-Eosin (H-E) staining. The degree of intestinal fibrosis was assessed by Masson staining and Sirius red staining. The expression of vimentin, α smooth muscle actin (α-SMA), type Ⅰ collagen, Ⅲ collagen and transforming growth factor-β1 (TGF-β1)/Smad3 in colon tissue was examined by immunohistochemistry. T test was performed for statistical analysis.
ResultsThe body mass of the transgenic DSS group decreased by (9.6±1.8)%, which was more than wild-type DSS group (6.2±1.3)%, the difference was statistically significant (t=3.751, P<0.01). The DAI score and colonic pathological score of transgenic DSS group were both higher than those of wild-type DSS group (7.33±0.58 vs. 6.00±1.00, and 14.00±1.05 vs. 11.75±0.50, respectively), and the differences were statistically significant (t=2.818 and 4.739, both P<0.05). The results of Masson staining and Sirius red staining showed aggravation of intestinal fibrosis. The results of immunohistochemical staining showed that the cumulative positive absorbance values of vimentin, α-SMA, TGF-β1 and Smad3 of wild-type DSS group were lower than those of transgenic DSS group (0.650±0.050 vs. 0.800±0.020, 0.390±0.040 vs. 0.600±0.040, 0.550±0.040 vs. 0.730±0.040, 0.590±0.020 vs. 0.830±0.040), and the differences were statistically significant (t=6.823, 9.093, 7.794 and 10.390, all P<0.01).
ConclusionTL1A may promote the proliferation and activation of fibroblasts through TGF-β1/Smad3 pathway, leading to the genesis and development of experimental colitis associated intestinal fibrosis.
Key words:
Inflammatory bowel diseases; Intestinal fibrosis; Tumor necrosis factor ligand-related molecule 1A
Contributor Information
Rongrong Zhan
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Dong Wang
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Wenxiu Jia
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Jia Song
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Mengyao Wu
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Hui Li
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Fengrong Yin
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Na Wang
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Chenxing Peng
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Hong Zhang
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Mei Song
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
Shuang Chen
Cedars-Sinai Medical Center, Department of Biomedical Sciences Immunology and Pediatric Immunization and Infectious Diseases, Los Angeles California 90001, USA
David Quan Shih
Cedars-Sinai Medical Center, Institute of Inflammatory Bowel Disease and Immunobiology, Los Angeles, California 90001, USA
Xiaolan Zhang
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang 050035, China
