Upregulated T4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice

Disrupted intestinal barrier homeostasis is fundamental to inflammatory bowel disease. Thymosin beta 4 (T beta 4) 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 T beta 4 by examining T beta 4 expression in a mouse model with dextran sodium sulfate (DSS)-induced colitis and colonic barrier damage. Additionally, we intraperitoneally injected C57BL/6 mice with T beta 4 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 T beta 4-induced barrier function and autophagy changes. Mucin2 levels decreased, microbial infiltration increased, and T beta 4 expression increased in the colitis mouse model versus the control mice, indicating mucus barrier damage. Moreover, T beta 4treated C57BL/6 mice had damaged intestinal mucus barriers and decreased LC3II levels. T beta 4 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, T beta 4 may be implicated in colitis by compromising the integrity of the intestinal mucus barrier and inhibiting autophagy. Thus, T beta 4 could be a new diagnostic marker for intestinal barrier defects.