Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis.

Ying Han,Tong Zhao,Xiang Cheng,Xiaomeng Wang,Dan Liu,Ming Zhao,Kuiwu Wu,Lingling Zhu,Ming Shi,Liang Guo,Ming Fan

doi:10.3389/fphys.2020.584508

Abstract

The cell adhesion molecule CHL1, which belongs to the immunoglobulin superfamily, functions in a variety of physiological and pathological processes, including neural development, tissue injury, and repair. We previously found that the loss of CHL1 exacerbated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we further addressed the role of CHL1 in mouse model of DSS-induced colitis and its’ potential mechanism. Colon tissues were collected from CHL1+/+, CHL1+/−, and CHL1−/− mice after DSS induction to investigate the effects of CHL1 on the development of colitis. The data showed that CHL1 was expressed in intestine tissue, and expression of CHL1 was increased by DSS-induced inflammation. CHL1 deficiency induced more pronounced colitis features, exacerbated inflammation, and damage to colonic tissues in DSS-induced mice. Moreover, colonic tissues of CHL1−/− mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice.

Highlights

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, idiopathic, relapsing disorder of the gastrointestinal tract (Xavier and Podolsky, 2007)
CHL1 deficiency exacerbated the development of dextran sulfate sodium (DSS)-induced colitis with pronounced colitis features, including an increase in proinflammatory cytokines and the leakage of fluorescein isothiocyanate (FITC) from the colon to the serum
These results suggested that CHL1 could be involved in regulating the occurrence and development of IBD (Figure 5)

Summary

Introduction

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, idiopathic, relapsing disorder of the gastrointestinal tract (Xavier and Podolsky, 2007). In UC, the pattern of inflammation of the colonic mucosa includes impairment of the immune response, breakdown of the epithelial barrier, and enhancement of the inflammatory process. The mechanisms of IBD remain unclear, this condition is viewed as the outcome of a multifactorial process, involving alterations in innate immunity and the immune response to bacteria, genetic predispositions, and some environmental factors (Gaya et al, 2006). It has been suggested that IBD is related to disorders of the innate immune response, adaptive immunity, endoplasmic reticulum stress, autophagy, intestinal epithelial barrier function, and microbial defense pathways (Liu et al, 2015). In patients with CD, the genes encoding adhesion molecules may lead to uncontrolled inflammation with ensuing destruction of epithelial cells, inappropriate stimulation of antimicrobial and T cell differentiation, and inflammasome events (Palmieri et al, 2015)

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