Effect of endoplasmic reticulum stress and acid-sensing ion channel 1a on the process of liver fibrosis

Abstract

Abstract: Acid-sensitive ion channels (ASICs) are a class of cationic channels activated by extracellular acidification protons (H+), with multiple subtypes permeable to different ions.Acid-sensing ion Channel 1a (ASIC1a) is one of the subtypes that allows Na+ and Ca2+ to flow into the cell and is expressed in inflammation, tumor and ischemic in the central nervous system and non-neuronal injury, but less reported in non-nervous systems. Endoplasmic reticulum(ER) unfolding or misfolding of protein accumulation and intracellular calcium homeostasis imbalance can lead to endoplasmic reticulum stress(ERS). In our early studies, ASIC1a and ERS were involved in the progression of liver fibrosis, but the exact pathway involved and whether there was a link between ASIC1a and ERS remain unkown. The purpose of this study was to explore the role of ASIC1a and ERS in the progression of hepatic fibrosis and the interaction between them. Results showed that the expression of ASIC1a and ERS-related proteins were increased in liver fibrosis and PDGF-BB induced HSCs, and there was potential link between them, which affected the ERS downstream pathway IRE1-XBP1. ASIC1a, stimulated by PDGF-BB, migrated to the cell membrane and activated, caused extracellular calcium influx, which can be regulated by PI3K / AKT pathway. ASIC1a activation induced calcium influx made intracellular calcium homeostasis changes, induced endoplasmic reticulum stress and IRE1-XBP1 pathway activation.