Role of Wnt/β-Catenin pathway agonist SKL2001 in Caerulein-induced acute pancreatitis

Objective: To clarify the protective role of Wnt/β-Catenin pathway agonist SKL2001 in Caerulein-induced acute pancreatitis (AP). Methods: AR42J cells and rats were divided into Control, Caerulein, SKL2001 + Caerulein and SKL2001 + Control groups respectively. Cell apoptosis was examined by flow cytometry. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of pancreas and small intestinal tissues. Inflammatory cytokines were detected by enzyme linked immunosorbent assay (ELISA) while Wnt/β-Catenin pathway-related genes by quantitative real-time PCR (qRT-PCR). Results: In-vitro results showed Caerulein promoted cell necrosis with inhibited Wnt/β-Catenin pathway and increased inflammatory cytokines. However, SKL2001 reduced cell necrosis and inflammatory cytokines with activation of Wnt/β-Catenin. Additionally, in-vivo results demonstrated 6 h after final Caerulein induction, accumulation of fluid or edema, hemorrhage, inflammation and necrosis of the pancreatic acini occurred and reached to maximal level at 12 h after final Caerulein induction; meanwhile, Wnt/β-Catenin pathway was evidently inhibited with enhanced inflammatory cytokines, and the above damages were further aggravated 12 h later. Nevertheless, the pancreatic and small intestinal tissue damages were alleviated in Caerulein-induced rats treated with SKL2001. Conclusion: Activation of Wnt/β-Catenin pathway could inhibit Caerulein-induced cell apoptosis and inflammatory cytokines release, thus improving pancreatic and intestinal damages of AP rats.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author