Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

Gelsolin (GSN) can sever actin filaments associated with autophagy. This study investigated how GSN-regulated actin filaments control autophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP). AP was produced in a rat model and PDECs using caerulein (CAE). Rat pancreatic duct tissue and HPDE6-C7 cells were extracted at 6, 12, 24, and 48 h after CAE treatment. HPDE6-C7 cells in the presence of CAE were treated with cytochalasin B (CB) or silenced for GSN for 24 h. Pancreatic histopathology and serum amylase levels were analyzed. Cellular ultrastructure and autophagy in PDECs were observed by transmission electron microscopy after 24 h of CAE treatment. The expression of GSN and autophagy markers LC3, P62, and LAMP2 was evaluated in PDECs by immunohistochemistry and western blotting. Actin filaments were observed microscopically. Amylase levels were highest at 6 h of AP, and pancreatic tissue damage increased over time. Mitochondrial vacuolization and autophagy were observed in PDECs. CAE increased GSN expression in these cells over time, increased the LC3-II/LC3-I ratio and LAMP2 expression at 24 and 6 h of treatment, respectively, and decreased P62 expression at all time points. CB treatment for 24 h decreased the LC3-II/LC3-I ratio and LAMP2 expression, increased P62 levels, but had no impact on GSN expression in CAE-treated PDECs. CAE induced actin depolymerization, and CB potentiated this effect. GSN silencing increased the LC3-II/LC3-I ratio and LAMP2 expression and reduced actin depolymerization in CAE-treated PDECs. GSN may inhibit autophagosome biogenesis and autophagosome-lysosome fusion by increasing actin depolymerization in PDECs in AP.

Bibliographic Details

Main Authors:	Yang,Huiying, Liang,Zhihai, Xie,Jinlian, Wu,Qing, Qin,Yingying, Zhang,Shiyu, Tang,Guodu
Format:	Digital revista
Language:	English
Published:	Associação Brasileira de Divulgação Científica 2023
Online Access:	http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100602
Tags:	Add Tag No Tags, Be the first to tag this record!