Upregulated Tβ4 expression in inflammatory bowel disease inhibits autophagy in mice

Evaluation of the effects of Thymosin β4 (Tβ4) on the intestinal mucus barrier in a mouse model of colitis suggest that Tβ4 may compromise the integrity of the mucus barrier and inhibit autophagy, identifying it as a potential diagnostic marker for intestinal barrier defects

Inflammatory bowel disease (IBD) is a chronic condition characterized by inflammation in the gastrointestinal tract. It includes two main subtypes: Crohn’s disease and ulcerative colitis. IBD is a complex and relapsing condition, and its exact causes are not yet fully understood. Common symptoms include abdominal pain, diarrhea, rectal bleeding, weight loss, fatigue, and fever. In addition, IBD is characterized by increased permeability of the paracellular space and defective regulation of tight junctions, leading to increased intestinal permeability.

The diagnosis of IBD is based on a combination of clinical symptoms, imaging studies, endoscopic findings, and histological examination. However, there is no gold standard diagnostic method for assessing intestinal barrier function. Therefore, the identification of molecular biomarkers to diagnose diseases associated with increased intestinal permeability is crucial. Several potential biomarkers, such as zonulin, fatty acid-binding proteins, citrulline, LPS-binding protein, and inflammatory factors, have been proposed, but a standardized diagnostic method has yet to be established.

The role of thymosin is multifaceted and extends to various physiological processes. Thymosin β4 is a peptide that is widely distributed in the body, including the thymus, spleen, brain, liver, kidney, and gastrointestinal tract. It has been found to play a vital role in promoting angiogenesis, enhancing endothelial progenitor cell viability, triggering cell proliferation and migration, and forming intracellular capillary-like structures. Tβ4 has also been shown to improve inflammation, possess cardioprotective effects, and promote skin wound healing. It has promising applications in treating dry eye diseases.

However, the specific effects of Tβ4 on the intestinal barrier are not fully understood. In a mouse model of colitis and colonic barrier damage, Tβ4 expression was found to increase, indicating mucus barrier damage. Tβ4-treated mice exhibited damaged intestinal mucus barriers and decreased autophagy, a molecular pathway that protects the endothelial barrier and regulates mucin secretion. Tβ4 inhibited colonic mucin2 production, disrupted tight junctions, and downregulated autophagy. These findings suggest that Tβ4 may be implicated in compromising the integrity of the intestinal mucus barrier and inhibiting autophagy, making it a potential new diagnostic marker for intestinal barrier defects.

The study highlights the need for standardized diagnostic methods and therapies targeting the intestinal barrier, as current methods are lacking. Identifying molecular biomarkers such as Tβ4 for diagnosing diseases associated with increased intestinal permeability is crucial.

In conclusion, this research article provides evidence of disrupted intestinal mucus barrier and increased Tβ4 expression in colitis in mice. Tβ4 is shown to impair the intestinal mucus barrier by inhibiting autophagy. The findings suggest that Tβ4 could serve as a potential diagnostic marker for identifying intestinal barrier damage in IBD. Further exploration of the underlying mechanisms and future studies are needed to fully understand the effects of Tβ4 on colitis.

Whole article can be found here: https://doi.org/10.1016/j.intimp.2023.111103