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

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.

CHL1-Deficient and Wild-Type Male Mice do Not Differ in Locomotor Recovery from Spinal Cord Injury

“…In this study, we found that CHL1−/− male mice did not show an improved functional recovery after spinal cord injury and they had no differences in the lesion volume compared to their CHL1+/+ littermates. This finding was surprising since we had published that CHL1−/− female mice had an improved functional recovery after SCI compared to their CHL1+/+ female littermates [ 18 ]. Based on previous reports mentioning an altered inflammation of CHL1−/− mice in mouse models of inflammatory bowel disease, we became interested in immune system-related functions after SCI.…”

“…Based on previous reports mentioning an altered inflammation of CHL1−/− mice in mouse models of inflammatory bowel disease, we became interested in immune system-related functions after SCI. Also, dextran sulfate-induced colitis was reported to lead to exacerbated inflammation and damage to colonic tissues of CHL1−/− mice with an increased neutrophil and macrophage infiltration [ 18 ]. In contrast, another group reported an attenuated inflammatory response of CHL1−/− mice in a dextran sulfate-induced inflammatory bowel disease mouse model [ 19 ].…”