Role and mechanism of tumor necrosis factor ligand-related molecule 1A in chronic experimental colitis associated intestinal fibrosis
10.3760/cma.j.issn.0254-1432.2019.07.004
- VernacularTitle:肿瘤坏死因子样配体1A在慢性实验性结肠炎相关肠纤维化中的作用与机制
- Author:
Rongrong ZHAN
1
;
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
Author Information
1. 河北医科大学第二医院消化内科 河北省消化病重点实验室 河北省消化病研究所
- Keywords:
Inflammatory bowel diseases;
Intestinal fibrosis;
Tumor necrosis factor ligand-related molecule 1A
- From:
Chinese Journal of Digestion
2019;39(7):452-457
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role and mechanism of tumor necrosis factor ligand -related molecule 1A (TL1A) in chronic experimental colitis associated intestinal fibrosis .Methods The 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, αsmooth 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.Results The 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).Conclusion TL1A 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 .
