TRIM21 alleviates acute pancreatitis cell injury and promotes efferocytosis by targeting CD47

Background: Acute pancreatitis (AP) is a debilitating inflammatory condition of the pancreas that significantly impacts patient health and quality of life. Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase predominantly expressed in the immune system, owns pivotal role in the pathogenesis of various diseases. Nevertheless the regulatory effects and underlying molecular mechanisms of TRIM21 in AP remain vague. Methods: Cholecystokinin (CCK) was utilized for evoking 266-6 cells to establish AP cell model. The protein expressions were inspected through western blot. The cell apoptosis and phagocytic index (%) were assessed through flow cytometry. Results: In this study, we established an AP cell model using 266-6 cells stimulated with cholecystokinin (CCK). Our results showed that TRIM21 expression was significantly reduced in the AP cell model, and its overexpression mitigated AP-induced cell damage by inhibiting apoptosis. Furthermore, TRIM21 overexpression enhanced macrophage efferocytosis and increased the efferocytosis rate from 20% to 32%. Mechanistically, we demonstrated that TRIM21 exerts its effects by downregulating the expression of Cluster of Differentiation 47 (CD47), and overexpression of CD47 partially rescued the regulatory effects of TRIM21. Conclusions: This study reveal that TRIM21 alleviates cell injury in AP and accelerates efferocytosis by targeting CD47, providing valuable insights into the TRIM21/CD47 axis as a potential therapeutic target in AP progression.

Acute pancreatitis; TRIM21; CD47; Efferocytosis

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