title: Protein misfolding and endoplasmic reticulum stress in chronic lung disease.
abstract: The pathogenesis of chronic lung disorders is poorly understood but is often thought to arise because of repeated injuries derived from exposure to exogenous or endogenous stress factors. Protein-misfolding events have been observed in a variety of genetic and nongenetic chronic lung disorders and may contribute to both the initiation and the progression of lung disease through endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Evidence indicates that exposure to common lung irritants such as cigarette smoke, environmental pollutants, and infectious viral or bacterial agents can induce ER stress and protein misfolding. Although the UPR is thought to be a molecular mechanism involved in the repair and restoration of protein homeostasis or "proteostasis," prolonged activation of the UPR may lead to compromised cellular functions, cellular transformation, or cell death. Here, we review literature that associates protein-misfolding events with ER stress and UPR activation and discuss how this basic molecular repair mechanism may contribute to the initiation and progression of various genetic and nongenetic chronic lung diseases.
authors.affiliation: Department of Medicine, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Medicine, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Department of Medicine, Hamilton, ON, Canada; McMaster Immunology Research Center, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Ehab A
authors.initials: EA
authors.lastname: Ayaub
authors.affiliation: Department of Medicine, Hamilton, ON, Canada; Hamilton Centre for Kidney Research, Hamilton, ON, Canada.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Dickhout
authors.affiliation: Department of Medicine, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, Hamilton, ON, Canada; McMaster Immunology Research Center, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Hamilton Centre for Kidney Research, Hamilton, ON, Canada. Electronic address: askkj@mcmaster.ca.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Ask
mesh_terms: D002908:Chronic Disease; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D008171:Lung Diseases / Q000503:physiopathology*; D058767:Protein Unfolding; D056811:Unfolded Protein Response / Q000502:physiology