Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF-κB pathway in hypertriglyceridemic acute pancreatitis.

Hypertriglyceridemic acute pancreatitis (HTGAP) is a clinical emergency. Tight junctions (TJs) and the cytoskeleton are essential for cell-cell junctions and cell survival, and although tricellulin is a key protein regulating cell junctions, its role in regulating TJ proteins and the cytoskeleton in pancreatic acinar cells in HTGAP is not currently clear. In the present study, 24 female hamsters were assigned to the control, hypertriglyceridemia (HTG), HTGAP and HTGAP + SC75741 groups. HTG was induced by a high-fat diet and HTGAP was established by retrograde sodium taurocholate injection. Serum triglyceride levels, pancreatic histopathological changes, and pancreatic expression of tricellulin, claudin-1 and NF-κB p65 were assessed. Furthermore, AR42J cell models with tricellulin overexpression and knockdown were cultured under HTG conditions, and protein levels were semi-quantified by western blotting. F-actin organization was assessed by immunofluorescence staining and intercellular morphology was examined by scanning electron microscopy. The results revealed that tricellulin expression was decreased and p65 expression was increased under hypertriglyceridemic conditions, whereas pancreatic histopathological injury was not significantly increased in the HTG group. The HTGAP group showed significantly more severe pancreatic injury than the control and HTG groups, accompanied by significantly decreased tricellulin and claudin-1 expression, and significantly increased p65 expression. After SC75741 (an inhibitor of the NF-κB signaling pathway) treatment, pancreatic injury and p65 expression were significantly decreased, whereas tricellulin and claudin-1 showed only partial recovery. In AR42J cells, tricellulin overexpression was associated with increased claudin-1 expression, reduced NF-κB activation, improved F-actin organization and better-preserved intercellular morphology, whereas tricellulin knockdown exhibited the opposite pattern. In conclusion, hypertriglyceridemic conditions were associated with impaired TJ integrity and cytoskeletal disorganization in pancreatic acinar cells, accompanied by reduced tricellulin expression and increased NF-κB activation. These findings suggest that tricellulin may contribute to HTGAP-related junctional and cytoskeletal injury, potentially involving NF-κB signaling.