Endoplasmic reticulum stress in acute lung injury and pulmonary fibrosis

Abstract

Pulmonary fibrosis (PF) is a progressive and irreversible lung disease that leads to diminished lung function, respiratory failure, and ultimately death and typically has a poor prognosis, with an average survival time of 2 to 5 years. Related articles suggested that endoplasmic reticulum (ER) stress played a critical role in the occurrence and progression of PF. The ER is responsible for maintaining protein homeostasis. However, factors such as aging, hypoxia, oxidative stress, or inflammation can disrupt this balance, promoting the accumulation of misfolded proteins in the ER and triggering ER stress. To cope with this situation, cells activate the unfolded protein response (UPR). Since acute lung injury (ALI) is one of the key onset events of PF, in this review, we will discuss the role of ER stress in ALI and PF by activating multiple signaling pathways and molecular mechanisms that affect the function and behavior of different cell types, with a focus on epithelial cells, fibroblasts, and macrophages. Linking ER stress to these cell types may broaden our understanding of the mechanisms underlying lung fibrosis and help us target these cells through these mechanisms. The relationship between ER stress and PF is still evolving, and future research will explore new strategies to regulate UPR pathways, providing novel therapeutic targets.