Abstract:Background and Aims Acute pancreatitis (AP) is an acute gastrointestinal emergency characterized by damage to pancreatic acinar cells and an inflammatory response. Circular RNAs (circRNAs) have been implicated in the regulation of various inflammatory disorders; however, the role of circSMARCA5 in AP remains unclear. This study aimed to investigate the function of circSMARCA5 and its underlying mechanism involving the miR-181-5p/LAMP-2 axis in AP.Methods An in vitro AP model was established by treating AR42J cells with cerulein. The expression levels of circSMARCA5, miR-181-5p, and LAMP-2 were determined by qRT-PCR. Cell viability was assessed using the MTT assay, and the levels of TNF-α, IL-1β, and IL-6 were measured by ELISA. Dual-luciferase reporter assays were performed to verify the interactions between circSMARCA5 and miR-181-5p as well as between miR-181-5p and LAMP-2. Gain-of-function and rescue experiments were conducted to evaluate their biological effects.Results CircSMARCA5 expression was significantly decreased, whereas miR-181-5p expression was markedly increased in cerulein-treated AR42J cells (all P<0.05). Overexpression of circSMARCA5 significantly enhanced cell viability and reduced the secretion of TNF-α, IL-1β, and IL-6 (all P<0.05). Dual-luciferase reporter assays confirmed that circSMARCA5 directly bound to miR-181-5p, while LAMP-2 was identified as a downstream target of miR-181-5p. Overexpression of miR-181-5p suppressed LAMP-2 expression, decreased cell viability, and aggravated inflammatory responses. These effects were partially reversed by circSMARCA5 or LAMP-2 overexpression.Conclusion CircSMARCA5 alleviates inflammatory injury in AP by acting as a competing endogenous RNA for miR-181-5p and thereby upregulating LAMP-2 expression. The circSMARCA5/miR-181-5p/LAMP-2 regulatory axis may represent a potential therapeutic target for AP.