Glycoprotein Nonmetastatic Melanoma Protein B: A Potential Therapeutic Target in Chronic Intestinal Fibrosis Induced by Dextran Sulfate Sodium

Abstract

Abstract Background: Intestinal fibrosis is a complication of inflammatory bowel disease (IBD). Currently, there are no effective preventive measures or medical therapies for intestinal fibrosis. Surgery remains the only available strategy in the management of fibro stenotic enteropathies. However, more than 50% of patients undergoing surgery experience recurrence of stenosis. We assessed effects of glycoprotein nonmetastatic melanoma protein B (Gpnmb) on chronic colonic fibrosis induced by dextran sulfate sodium (DSS) in mice. Materials and Methods: GSE42768 mRNA microarray dataset was selected to carry out GEO2R bioinformatics analysis to predict differentially expressed genes. Chronic colonic inflammation-associated fibrosis was induced by DSS in mice. Twenty-four healthy male BALB/c were assigned to four groups: Control, model, T1: Intragastric administration of Thalidomide (Thal) 100 mg/kg.day beginning at day 18, T2: Intragastric administration of Thal (100 mg/kg.day) beginning at day 0 (n = 6 in each group). The colon was removed after modeling and assessed by pathological staining, Western blot, and reverse-transcription polymerase chain reaction. Col1α2, Gpnmb, Wnt1, and β-catenin antibodies were used. Results: The degree of chronic colitis and fibrosis was highest in the model group, and lowest in the control group. Thal treatment significantly alleviated DSS-induced chronic colitis and intestinal fibrosis, decreasing Gpnmb at both mRNA and Western blot levels. Expressions of Col1α2, Wnt1, and β-catenin got the same results. Conclusions: From bioinformatic analysis and fundamental experiment, we have illustrated that Gpnmb may stimulate the occurrence of intestinal fibrosis via Wnt1/β-catenin pathway. It may be a new therapeutic target for IBD-related intestinal fibrosis.