The expression of ASK1 and its impact on intestinal epithelial barrier function and inflammatory response in Crohn's disease
10.13431/j.cnki.immunol.j.20250005
- VernacularTitle:ASK1在克罗恩病中的表达及其对肠上皮屏障功能和炎症反应的影响
- Author:
Xingchao ZHU
1
;
Jingrong XIANG
;
Jiayu WANG
;
Huan ZHANG
;
Jie FENG
;
Tongguo SHI
;
Qinhua XI
Author Information
1. 215000,苏州大学附属第一医院消化内科
- Publication Type:Journal Article
- Keywords:
Crohn's disease;
Apoptosis signal-regulating kinase 1;
Intestinal epithelial barrier;
Krüppel-like factor 4
- From:
Immunological Journal
2025;41(1):36-43
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.
