Gelsolin Impairs Barrier Function in Pancreatic Ductal Epithelial Cells by Actin Filament Depolymerization in Hypertriglyceridemia-Induced Pancreatitis in Vitro

Abstract Gelsolin (GSN) is a calcium-regulated actin-binding protein that can sever actin filaments. Actin dynamics affects the function and integrity of epithelial barriers. This study investigated the role of GSN on barrier function in pancreatic ductal epithelial cells (PDECs) in hypertriglyceridemia-induced pancreatitis (HTGP).The human PDEC cell line HPDE6-C7 was silenced for GSN and treated with caerulein (CAE) + triglycerides (TG). Intracellular calcium levels and the actin filament network were analyzed under a fluorescence microscope. The expression of GSN, E-cadherin, nectin-2, ZO-1, and occludin was evaluated by quantitative real-time polymerase chain reaction and western blotting. Ultrastructural changes in tight junctions (TJs) were observed by transmission electron microscopy. The permeability of PDECs was analyzed by fluorescein isothiocyanate-dextran fluorescence. The results showed that CAE + TG increased intracellular calcium levels, actin filament depolymerization, and GSN expression, and increased PDEC permeability by decreasing the expression of E-cadherin, nectin-2, ZO-1, and occludin compared with CAE alone. Moreover, changes in these markers, except for intracellular calcium levels, were reversed by silencing GSN. Based on these results, it can be concluded that GSN disrupts barrier function in PDECs by causing actin filament depolymerization in HTGP in vitro.