Hui-Jing Zhang1, Yi-Ning Zhang1, Huan Zhou1, Lin Guan1, Yue Li1, Ming-Jun Sun2. 1. Department of Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China. 2. Department of Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China. sunmingjun2175@hotmail.com.
Abstract
BACKGROUND: Intestinal fibrosis is a common complication of Crohn's disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial-mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported. AIMS: To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT. METHODS: In this study, we evaluated the expression of IL-17A and EMT-related genes in colonic mucosal biopsy tissues of CD patients and control individuals. Then, we examined the changes of EMT-related genes and fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing concentrations of IL-17A or with TGF-β1, to verify the potential inductive effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo. RESULTS: We found the occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CD patients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal epithelial cells that come with reduced E-cadherin expression and increased expression of vimentin, snail, and α-SMA. We further found that anti-IL-17A treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine. CONCLUSIONS: Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.
BACKGROUND:Intestinal fibrosis is a common complication of Crohn's disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial-mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported. AIMS: To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT. METHODS: In this study, we evaluated the expression of IL-17A and EMT-related genes in colonic mucosal biopsy tissues of CDpatients and control individuals. Then, we examined the changes of EMT-related genes and fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing concentrations of IL-17A or with TGF-β1, to verify the potential inductive effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo. RESULTS: We found the occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CDpatients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal epithelial cells that come with reduced E-cadherin expression and increased expression of vimentin, snail, and α-SMA. We further found that anti-IL-17A treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine. CONCLUSIONS: Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.
Authors: S Videla; J Vilaseca; C Medina; M Mourelle; F Guarner; A Salas; J-R Malagelada Journal: J Pharmacol Exp Ther Date: 2005-10-27 Impact factor: 4.030
Authors: Ian C Lawrance; Feng Wu; André Z A Leite; Joseph Willis; Gail A West; Claudio Fiocchi; Shukti Chakravarti Journal: Gastroenterology Date: 2003-12 Impact factor: 22.682
Authors: G Latella; R Sferra; A Vetuschi; G Zanninelli; A D'Angelo; V Catitti; R Caprilli; E Gaudio Journal: Eur J Clin Invest Date: 2008-06 Impact factor: 4.686
Authors: Jacques Cosnes; Anne Bourrier; Isabelle Nion-Larmurier; Harry Sokol; Laurent Beaugerie; Philippe Seksik Journal: Gut Date: 2012-03-02 Impact factor: 23.059
Authors: Jie Wang; Sinan Lin; Jonathan Mark Brown; David van Wagoner; Claudio Fiocchi; Florian Rieder Journal: Immunol Rev Date: 2021-05-16 Impact factor: 10.983
Authors: Brecht Creyns; Jonathan Cremer; Tomoaki Hoshino; Karel Geboes; Gert de Hertogh; Marc Ferrante; Séverine Vermeire; Jan L Ceuppens; Gert Van Assche; Christine Breynaert Journal: Sci Rep Date: 2019-07-11 Impact factor: 4.379