Upregulated Tβ4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice

Abstract

Disrupted intestinal barrier homeostasis is fundamental to inflammatory bowel disease. Thymosin β4 (Tβ4) improves inflammation and has beneficial effects in dry-eye diseases, but its effects on the intestinal mucus barrier remain unknown. Therefore, this study evaluated the underlying regulatory mechanisms and effects of Tβ4 by examining Tβ4 expression in a mouse model with dextran sodium sulfate (DSS)-induced colitis and colonic barrier damage. Additionally, we intraperitoneally injected C57BL/6 mice with Tβ4 to assess barrier function, microtubule-associated protein 1 light chain 3 (LC3II) protein expression, and autophagy. Finally, normal human colon tissue and colon carcinoma cells (Caco2) were cultured to verify Tβ4-induced barrier function and autophagy changes. Mucin2 levels decreased, microbial infiltration increased, and Tβ4 expression increased in the colitis mouse model versus the control mice, indicating mucus barrier damage. Moreover, Tβ4-treated C57BL/6 mice had damaged intestinal mucus barriers and decreased LC3II levels. Tβ4 also inhibited colonic mucin2 production, disrupted tight junctions, and downregulated autophagy; these results were confirmed in Caco2 cells and normal human colon tissue. In summary, Tβ4 may be implicated in colitis by compromising the integrity of the intestinal mucus barrier and inhibiting autophagy. Thus, Tβ4 could be a new diagnostic marker for intestinal barrier defects.

Keywords: Autophagy; Inflammatory bowel disease; Intestinal epithelial cells; Mucin2; Mucus barrier; Thymosin β4.