Abstract
Inflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Interestingly, Pin1 knockout (KO) mice exhibited significant attenuation of DSS-induced colitis compared to wild-type (WT) mice, based on various parameters, including body weight, colon length, microscopic observation of the intestinal mucosa, inflammatory cytokine expression, and cleaved caspase-3. In addition, a role of Pin1 in inflammation was suggested because the percentage of M1-type macrophages in the colon was decreased in the Pin1 KO mice while that of M2-type macrophages was increased. Moreover, Pin1 KO mice showed downregulation of both Il17 and Il23a expression in the colon, both of which have been implicated in the development of colitis. Finally, oral administration of Pin1 inhibitor partially but significantly prevented DSS-induced colitis in mice, raising the possibility of Pin1 inhibitors serving as therapeutic agents for IBD.
Highlights
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are serious disorders
prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein expression levels in the colons of mice treated with dextran sodium sulfate (DSS) for 7 days were dramatically increased, i.e., by approximately 45 folds, as compared with those of control mice, while Pin1 mRNA levels were not significantly altered (Figure 1A,B)
These results suggest that the Pin1 inhibitor exerts therapeutic effects on DSS-induced colitis in mice, raising the possibility of Pin1 serving as a novel therapeutic target for IBD
Summary
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are serious disorders. The pathophysiology underlying these diseases has yet to be fully clarified. IBDs are chronic relapsing disorders characterized pathologically by inflammation and epithelial injury involving the gastrointestinal tract. Genetic and environmental risk factors trigger epithelial barrier function deterioration [3,4]. Impaired barrier function results in the invasion of commensal bacteria from the gut lumen into the bowel wall, which leads to immune cell activation and cytokine production [5,6]. Chronic inflammation leads to disease complications as well as tissue destruction, both of which are driven by mucosal cytokine responses
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