ARRB1 reverses 5-FU-induced chemotherapeutic intestinal mucosal injury by protecting intestinal barrier and stem cell function

Abstract

Chemotherapy-induced intestinal mucosal injury(CIMI)is a common side effect of chemotherapy, and its mechanism is complex. Previous studies have demonstrated that Armillariella tabescens polysaccharides (ATPS) exert intestinal mucosal protective effects by upregulating tight junction protein expression and reducing apoptosis of intestinal epithelial cells, and the expression of β-arrestin 1 (ARRB 1) is altered during this process. The aim of this study was to investigate the role of ARRB 1 in ATPS protection against chemotherapeutic intestinal mucosal injury induced by 5-fluorouracil (5-FU). A CIMI model was established by intraperitoneal injection of 5-FU (50 mg/kg), and ATPS (200 mg/kg) was administered by gavage once a day for treatment. Body weight changes of mice were monitored. The gross appearance of intestinal tissues was observed, and hematoxylin and eosin staining was performed for histological analysis and histological activity score. Immunohistochemistry was performed to detect the expression of tight junction ( TJ ) protein markers. Organoid cultures were performed to detect the status of intestinal stem cells. The results showed that ATPS ameliorated 5-FU-induced intestinal inflammation in WT mice by increasing body weight, reducing histopathological damage, and increasing intestinal tight junction protein expression, and organoid formation rate. However, the alleviating effect of ATPS on CIMI was not significant in ARRB1-KO mice. Therefore, we suggest that ARRB1 is involved in the repair of CIMI damage by ATPS, and the mechanism may be related to the regulation of small intestinal tissue TJ protein production by ARRB1 to protect intestinal stem cells from chemotherapeutic damage.