Elevated expression of circular RNA circ0001415 attenuates acinar cell pyroptosis during acute pancreatitis.

Abstract

Introduction: Pyroptosis, a form of inflammatory programmed cell death, is implicated in acute pancreatitis (AP). Acinar cell pyroptosis plays a pivotal role in the pathogenesis of AP. Circular RNA has emerged as an important regulatory molecule in AP; however, its specific function and mechanism in modulating acinar cell pyroptosis during AP are unknown.

Methods: Healthy male C57BL/6 mice were divided into control group and acute pancreatitis group. Cell experiments are also divided into two groups: control group and drug-treated (caerulein and lipopolysaccharide) group. Tissue detection was used hematoxylin-eosin staining. Serum analysis was assessed by Enzyme-linked immunosorbent assay (ELISA). Differential expression of circRNA in pancreatic head tissue was screened using RNA-sequencing and circ0001415 was validated by real-time PCR. immunofluorescence, Western blot assay, ELISA, and real-time PCR were performed to detect cell pyroptosis in the mice and caerulein and lipopolysaccharide-induced pancreatic acinar cell line MPC-83 cell models. Gene knockdown and Luciferase reporter assay was used to confirm the regulatory role of circRNA0001415 in acinar cell pyroptosis.

Results: We found that circ0001415 is significantly upregulated in the pancreatic head tissue of these mice. Subsequent experiments indicated that circ0001415 likely serves as a molecular sponge for microRNA-1946a, thereby potentially enhancing the expression levels of the pyroptosis-associated protein caspase 1. Consequently, circ0001415 upregulation appears to counteract the decrease in acinar cell pyroptosis observed in AP. In vitro studies revealed that the knockdown of circ0001415 intensified the pyroptosis of acinar cells induced by lipopolysaccharide and caerulein.

Conclusion: These findings provide novel insights suggesting that the upregulation of circ0001415 may serve as a protective mechanism against the dampening effects on acinar cell pyroptosis following AP. Overall, circ0001415 is a potential molecular target for AP treatment.