Understanding the Impact of ER Stress on Lung Physiology

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2025 Jan 2

PMID 39744015

Authors

Zhiling Fu

Wei Wang

Yuan Gao

Affiliations

Soon will be listed here.

Abstract

Human lungs consist of a distinctive array of cell types, which are subjected to persistent challenges from chemical, mechanical, biological, immunological, and xenobiotic stress throughout life. The disruption of endoplasmic reticulum (ER) homeostatic function, triggered by various factors, can induce ER stress. To overcome the elevated ER stress, an adaptive mechanism known as the unfolded protein response (UPR) is activated in cells. However, persistent ER stress and maladaptive UPR can lead to defects in proteostasis at the cellular level and are typical features of the lung aging. The aging lung and associated lung diseases exhibit signs of ER stress-related disruption in cellular homeostasis. Dysfunction resulting from ER stress and maladaptive UPR can compromise various cellular and molecular processes associated with aging. Hence, comprehending the mechanisms of ER stress and UPR components implicated in aging and associated lung diseases could enable to develop appropriate therapeutic strategies for the vulnerable population.

References

Luthers C, Dunn T, Snow A . ORMDL3 and Asthma: Linking Sphingolipid Regulation to Altered T Cell Function. Front Immunol. 2021; 11:597945. PMC: 7793773. DOI: 10.3389/fimmu.2020.597945. View

Nagasaki T, Matsumoto H . Influences of smoking and aging on allergic airway inflammation in asthma. Allergol Int. 2013; 62(2):171-9. DOI: 10.2332/allergolint.12-RA-0523. View

Xia S, Wang Z, Sun S, Su Y, Li Z, Shao J . Endoplasmic reticulum stress and protein degradation in chronic liver disease. Pharmacol Res. 2020; 161:105218. DOI: 10.1016/j.phrs.2020.105218. View

Franceschi C, Campisi J . Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014; 69 Suppl 1:S4-9. DOI: 10.1093/gerona/glu057. View

Lin F, Liao C, Zhang J, Sun Y, Lu W, Bai Y . Hydrogen Sulfide Inhibits Bronchial Epithelial Cell Epithelial Mesenchymal Transition Through Regulating Endoplasm Reticulum Stress. Front Mol Biosci. 2022; 9:828766. PMC: 9039047. DOI: 10.3389/fmolb.2022.828766. View

Aghali A, Koloko Ngassie M, Pabelick C, Prakash Y . Cellular Senescence in Aging Lungs and Diseases. Cells. 2022; 11(11). PMC: 9179897. DOI: 10.3390/cells11111781. View

Lei Y, Yu H, Ding S, Liu H, Liu C, Fu R . Molecular mechanism of ATF6 in unfolded protein response and its role in disease. Heliyon. 2024; 10(5):e25937. PMC: 10907738. DOI: 10.1016/j.heliyon.2024.e25937. View

Dwyer M, Pasini M, De Dominicis S, Righi E . Physical activity: Benefits and challenges during the COVID-19 pandemic. Scand J Med Sci Sports. 2020; 30(7):1291-1294. PMC: 7323175. DOI: 10.1111/sms.13710. View

Korhonen P, Helenius M, Salminen A . Age-related changes in the regulation of transcription factor NF-kappa B in rat brain. Neurosci Lett. 1997; 225(1):61-4. DOI: 10.1016/s0304-3940(97)00190-0. View

10.

Cao S, Kaufman R . Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid Redox Signal. 2014; 21(3):396-413. PMC: 4076992. DOI: 10.1089/ars.2014.5851. View

11.

Martino M, Olsen J, Fulcher N, Wolfgang M, ONeal W, Ribeiro C . Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1. J Biol Chem. 2009; 284(22):14904-13. PMC: 2685672. DOI: 10.1074/jbc.M809180200. View

12.

Harman D . Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3):298-300. DOI: 10.1093/geronj/11.3.298. View

13.

Wang Q, Yang L, Peng Y, Gao M, Yang M, Xing W . Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation. Mediators Inflamm. 2019; 2019:6453296. PMC: 6409002. DOI: 10.1155/2019/6453296. View

14.

Rawlins E, Okubo T, Xue Y, Brass D, Auten R, Hasegawa H . The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell. 2009; 4(6):525-34. PMC: 2730729. DOI: 10.1016/j.stem.2009.04.002. View

15.

Tagawa Y, Hiramatsu N, Kato H, Sakoh T, Nakajima S, Hayakawa K . Induction of CCAAT/enhancer-binding protein-homologous protein by cigarette smoke through the superoxide anion-triggered PERK-eIF2α pathway. Toxicology. 2011; 287(1-3):105-12. DOI: 10.1016/j.tox.2011.06.005. View

16.

Nijholt D, de Graaf T, van Haastert E, Oliveira A, Berkers C, Zwart R . Endoplasmic reticulum stress activates autophagy but not the proteasome in neuronal cells: implications for Alzheimer's disease. Cell Death Differ. 2011; 18(6):1071-81. PMC: 3131935. DOI: 10.1038/cdd.2010.176. View

17.

Cai Y, Pi W, Sivaprakasam S, Zhu X, Zhang M, Chen J . UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development. PLoS Genet. 2015; 11(11):e1005643. PMC: 4636156. DOI: 10.1371/journal.pgen.1005643. View

18.

Erickson R, Dunning L, Holtzman J . The effect of aging on the chaperone concentrations in the hepatic, endoplasmic reticulum of male rats: the possible role of protein misfolding due to the loss of chaperones in the decline in physiological function seen with age. J Gerontol A Biol Sci Med Sci. 2006; 61(5):435-43. DOI: 10.1093/gerona/61.5.435. View

19.

Rock J, Onaitis M, Rawlins E, Lu Y, Clark C, Xue Y . Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A. 2009; 106(31):12771-5. PMC: 2714281. DOI: 10.1073/pnas.0906850106. View

20.

Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G . Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res. 2021; 22(1):109. PMC: 8052779. DOI: 10.1186/s12931-021-01711-1. View