Expression of Stress-Induced Genes in Bronchoalveolar Lavage Cells and Lung Fibroblasts from Healthy and COPD Subjects

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 27

PMID 38928305

Authors

Martin Garcia-Ryde

Nicole M D van der Burg

Frida Berlin

Gunilla Westergren-Thorsson

Leif Bjermer

Jaro Ankerst

Anna-Karin Larsson-Callerfelt

Cecilia K Andersson

Ellen Tufvesson

Affiliations

Soon will be listed here.

Abstract

Chronic obstructive pulmonary disease (COPD) is commonly caused from smoking cigarettes that induce biological stress responses. Previously we found disorganized endoplasmic reticulum (ER) in fibroblasts from COPD with different responses to chemical stressors compared to healthy subjects. Here, we aimed to investigate differences in stress-related gene expressions within lung cells from COPD and healthy subjects. Bronchoalveolar lavage (BAL) cells were collected from seven COPD and 35 healthy subjects. Lung fibroblasts were derived from 19 COPD and 24 healthy subjects and exposed to cigarette smoke extract (CSE). Gene and protein expression and cell proliferation were investigated. Compared to healthy subjects, we found lower gene expression of CHOP in lung fibroblasts from COPD subjects. Exposure to CSE caused inhibition of lung fibroblast proliferation in both groups, though the changes in ER stress-related gene expressions (ATF6, IRE1, PERK, ATF4, CHOP, BCL2L1) and genes relating to proteasomal subunits mostly occurred in healthy lung fibroblasts. No differences were found in BAL cells. In this study, we have found that lung fibroblasts from COPD subjects have an atypical ER stress gene response to CSE, particularly in genes related to apoptosis. This difference in response to CSE may be a contributing factor to COPD progression.

References

Lozon T, Eastman A, Matute-Bello G, Chen P, Hallstrand T, Altemeier W . PKR-dependent CHOP induction limits hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2010; 300(3):L422-9. PMC: 3064291. DOI: 10.1152/ajplung.00166.2010. View

Dombroski B, Nayak R, Ewens K, Ankener W, Cheung V, Spielman R . Gene expression and genetic variation in response to endoplasmic reticulum stress in human cells. Am J Hum Genet. 2010; 86(5):719-29. PMC: 2869002. DOI: 10.1016/j.ajhg.2010.03.017. View

Zhang Y, Li T, Pan M, Wang W, Huang W, Yuan Y . SIRT1 prevents cigarette smoking-induced lung fibroblasts activation by regulating mitochondrial oxidative stress and lipid metabolism. J Transl Med. 2022; 20(1):222. PMC: 9107262. DOI: 10.1186/s12967-022-03408-5. View

Wrench C, Baker J, Monkley S, Fenwick P, Murray L, Donnelly L . Small airway fibroblasts from patients with chronic obstructive pulmonary disease exhibit cellular senescence. Am J Physiol Lung Cell Mol Physiol. 2023; 326(3):L266-L279. PMC: 11281792. DOI: 10.1152/ajplung.00419.2022. View

Weidner J, Jarenback L, Aberg I, Westergren-Thorsson G, Ankerst J, Bjermer L . Endoplasmic reticulum, Golgi, and lysosomes are disorganized in lung fibroblasts from chronic obstructive pulmonary disease patients. Physiol Rep. 2018; 6(5). PMC: 5827558. DOI: 10.14814/phy2.13584. View

Aksoy M, Kim V, Cornwell W, Rogers T, Kosmider B, Bahmed K . Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers. Respir Res. 2017; 18(1):78. PMC: 5414124. DOI: 10.1186/s12931-017-0561-6. View

Rahman I, Biswas S, Kode A . Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol. 2006; 533(1-3):222-39. DOI: 10.1016/j.ejphar.2005.12.087. View

Garcia-Ryde M, van der Burg N, Larsson C, Larsson-Callerfelt A, Westergren-Thorsson G, Bjermer L . Lung Fibroblasts from Chronic Obstructive Pulmonary Disease Subjects Have a Deficient Gene Expression Response to Cigarette Smoke Extract Compared to Healthy. Int J Chron Obstruct Pulmon Dis. 2023; 18:2999-3014. PMC: 10742772. DOI: 10.2147/COPD.S422508. View

Song M, Peng H, Guo W, Luo M, Duan W, Chen P . Cigarette Smoke Extract Promotes Human Lung Myofibroblast Differentiation by the Induction of Endoplasmic Reticulum Stress. Respiration. 2019; 98(4):347-356. DOI: 10.1159/000502099. View

10.

Kode A, Rajendrasozhan S, Caito S, Yang S, Megson I, Rahman I . Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2007; 294(3):L478-88. DOI: 10.1152/ajplung.00361.2007. View

11.

Brandsma C, Timens W, Jonker M, Rutgers B, Noordhoek J, Postma D . Differential effects of fluticasone on extracellular matrix production by airway and parenchymal fibroblasts in severe COPD. Am J Physiol Lung Cell Mol Physiol. 2013; 305(8):L582-9. DOI: 10.1152/ajplung.00152.2013. View

12.

Malmstrom J, Larsen K, Hansson L, Lofdahl C, Marko-Varga G, Westergren-Thorsson G . Proteoglycan and proteome profiling of central human pulmonary fibrotic tissue utilizing miniaturized sample preparation: a feasibility study. Proteomics. 2002; 2(4):394-404. DOI: 10.1002/1615-9861(200204)2:4<394::AID-PROT394>3.0.CO;2-6. View

13.

Tufvesson E, Nihlberg K, Westergren-Thorsson G, Bjermer L . Leukotriene receptors are differently expressed in fibroblast from peripheral versus central airways in asthmatics and healthy controls. Prostaglandins Leukot Essent Fatty Acids. 2011; 85(2):67-73. DOI: 10.1016/j.plefa.2011.04.025. View

14.

Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M . Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008; 178(8):838-46. PMC: 2566794. DOI: 10.1164/rccm.200802-313OC. View

15.

Okuda T, Wakaguri H, Suzuki Y, Sugano S . Monitoring endoplasmic reticulum stress responsive mRNAs by RNA sequencing. Gene. 2012; 500(1):63-72. DOI: 10.1016/j.gene.2012.03.048. View

16.

Ya Brodsky W . Protein synthesis rhythm. J Theor Biol. 1975; 55(1):167-200. DOI: 10.1016/s0022-5193(75)80115-9. View

17.

Kanaji N, Basma H, Nelson A, Farid M, Sato T, Nakanishi M . Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes. Am J Physiol Lung Cell Mol Physiol. 2014; 307(5):L364-73. DOI: 10.1152/ajplung.00041.2014. View

18.

Min T, Bodas M, Mazur S, Vij N . Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema. J Mol Med (Berl). 2011; 89(6):577-93. PMC: 3128462. DOI: 10.1007/s00109-011-0732-8. View

19.

Yeap J, Hyder Ali I, Ibrahim B, Tan M . Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets. Pulm Pharmacol Ther. 2023; 81:102218. DOI: 10.1016/j.pupt.2023.102218. View

20.

Krimmer D, Burgess J, Wooi T, Black J, Oliver B . Matrix proteins from smoke-exposed fibroblasts are pro-proliferative. Am J Respir Cell Mol Biol. 2011; 46(1):34-9. DOI: 10.1165/rcmb.2010-0426OC. View