Angiopoietin-like 4 knockdown attenuates cigarette smoke extract–induced oxidative stress and apoptosis in lung bronchial epithelial cells by inhibiting NADPH oxidase
Main Article Content
Keywords
ANGPTL4, lung bronchial epithelial cells, NAPDH oxidase, cigarette smoke extract, oxidative stress
Abstract
It has been found that angiopoietin-like 4 (ANGPTL4) expression is increased in the serum of patients with chronic obstructive pulmonary disease (COPD). Herein, cigarette smoke extract (CSE) was used to stimulate oxidative stress in bronchial epithelial cells BEAS-2B, and the role and potential mechanism of ANGPTL4 in smoking-induced lung dysfunction were explored. The roles of different concentrations of CSE (0, 1, 2.5, 5, or 10%) in cell viability and ANGPTL4 levels were evaluated. Following ANGPTL4 being knocked down, the effects of ANGPTL4 knockdown on oxidative stress and apoptosis were determined. Moreover, the level of NADPH oxidase 2 (NOX2) was upregulated to assess the mediated role of NOX in the regulation of ANGPTL4, along with JNK/p38 MAPK signaling. CSE treatment elevated the level of ANGPTL4, and ANGPTL4 knockdown reduced CSE-induced oxidative stress, apoptosis, and NOX level in BEAS-2B cells. The greatest degree of alteration was found in NOX2, and additional NOX2 overexpression broke the inhibitory influences of ANGPTL4 knockdown on oxidative stress and apoptosis. Otherwise, ANGPTL4 knockdown hindered the activation of JNK/p38 MAPK signaling, whereas NOX2 overexpression activated this signaling pathway. Together, ANGPTL4 knockdown attenuated CSE-induced oxidative stress, apoptosis, and activation of JNK/MAPK signaling by inhibiting NOX.
References
1. Mendy A, Salo PM, Cohn RD, Wilkerson J, Zeldin DC, Thorne PS. House dust endotoxin association with chronic bronchitis and emphysema. Environ Health Perspect. 2018 Mar 23;126(3):37007. 10.1289/EHP2452
2. Raju SV, Kim H, Byzek SA, Tang LP, Trombley JE, Jackson P, et al. A ferret model of COPD-related chronic bronchitis. JCI Insight. 2016 Sep 22;1(15):e87536. 10.1172/jci.insight.87536
3. Zhang J, Xu Q, Sun W, Zhou X, Fu D, Mao L. New insights into the role of NLRP3 inflammasome in pathogenesis and treatment of chronic obstructive pulmonary disease. J Inflam Res. 2021;14:4155–4168. 10.2147/JIR.S324323
4. Dransfield MT, Kunisaki KM, Strand MJ, Anzueto A, Bhatt SP, Bowler RP, et al. Acute exacerbations and lung function loss in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017 Feb 1;195(3):324–330.
5. Wang J, Li Y, Zhao P, Tian Y, Liu X, He H, et al. Exposure to air pollution exacerbates inflammation in rats with preexisting COPD. Mediat Inflam. 2020;2020:4260204. 10.1155/2020/4260204
6. Yamada H, Hida N, Masuko H, Sakamoto T, Hizawa N. Effects of lung function-related genes and TSLP on COPD phenotypes. Copd. 2020 Feb;17(1):59–64. 10.1080/15412555.2019.1708296
7. Cipollina C, Bruno A, Fasola S, Cristaldi M, Patella B, Inguanta R, et al. Cellular and molecular signatures of oxidative stress in bronchial epithelial cell models injured by cigarette smoke extract. Int J Mol Sci. 2022 Feb 4;23(3):1770. 10.3390/ijms23031770
8. Bodas M, Van Westphal C, Carpenter-Thompson R, Mohanty DK, Vij N. Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment. Free Radic Biol Med. 2016 Aug;97:441–453. 10.1016/j.freeradbiomed.2016.06.017
9. Dang X, He B, Ning Q, Liu Y, Guo J, Niu G, et al. Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways. Respir Res. 2020 Apr 22;21(1):95. 10.1186/s12931-020-01358-4
10. Guan R, Wang J, Cai Z, Li Z, Wang L, Li Y, et al. Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway. Redox Biol. 2020 Jan;28:101356. 10.1016/j.redox.2019.101356
11. Fernández-Hernando C, Suárez Y. ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis. Curr Opin Hematol. 2020 May;27(3):206–213. 10.1097/MOH.0000000000000580
12. Yang J, Li X, Xu D. Research progress on the involvement of ANGPTL4 and loss-of-function variants in lipid metabolism and coronary heart disease: is the “prime time” of ANGPTL4-targeted therapy for coronary heart disease approaching? Cardiovasc Drugs Therapy. 2021 Jun;35(3):467–477. 10.1007/s10557-020-07001-0
13. Aryal B, Price NL, Suarez Y, Fernández-Hernando C. ANGPTL4 in metabolic and cardiovascular disease. Trends Mol Med. 2019 Aug;25(8):723–734. 10.1016/j.molmed.2019.05.010
14. Alex S, Lange K, Amolo T, Grinstead JS, Haakonsson AK, Szalowska E, et al. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol Cell Biol. 2013 Apr;33(7):1303–1316. 10.1128/MCB.00858-12
15. Yang X, Cheng Y, Su G. A review of the multifunctionality of angiopoietin-like 4 in eye disease. Biosci Rep. 2018 Oct 31;38(5):BSR20180557. 10.1042/BSR20180557
16. Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, et al. Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing. J Biol Chem. 2010 Oct 22;285(43):32999–33009. 10.1074/jbc.M110.108175
17. Ruscica M, Zimetti F, Adorni MP, Sirtori CR, Lupo MG, Ferri N. Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia. Pharmacol Res. 2020 Mar;153:104653. 10.1016/j.phrs.2020.104653
18. Oteng AB, Ruppert PMM, Boutens L, Dijk W, van Dierendonck X, Olivecrona G, et al. Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice. J Lipid Res. 2019 Oct;60(10):1741–1754. 10.1194/jlr.M094128
19. Raschke S, Eckel J. Adipo-myokines: two sides of the same coin—mediators of inflammation and mediators of exercise. Mediat Inflam. 2013;2013:320724. 10.1155/2013/320724
20. Kang YT, Li CT, Tang SC, Hsin IL, Lai YC, Hsiao YP, et al. Nickel chloride regulates ANGPTL4 via the HIF-1α-mediated TET1 expression in lung cells. Toxicol Lett. 2021 Nov 1;352:17–25. 10.1016/j.toxlet.2021.09.007
21. Saito M, Mitani A, Ishimori T, Miyashita N, Isago H, Mikami Y, et al. Active mTOR in lung epithelium promotes epithelial-mesenchymal transition and enhances lung fibrosis. Am J Respir Cell Mol Biol. 2020 Jun;62(6):699–708. 10.1165/rcmb.2019-0255OC
22. Waschki B, Kirsten AM, Holz O, Meyer T, Lichtinghagen R, Rabe KF, et al. Angiopoietin-like protein 4 and cardiovascular function in COPD. BMJ Open Respir Res. 2016;3(1):e000161. 10.1136/bmjresp-2016-000161
23. Li L, Foo BJW, Kwok KW, Sakamoto N, Mukae H, Izumikawa K, et al. Antibody treatment against angiopoietin-like 4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia. mBio. 2019 Jun 4;10(3):e02469. 10.1128/mBio.02469-18
24. Song B, Ye L, Wu S, Jing Z. Long non-coding RNA MEG3 regulates CSE-induced apoptosis and inflammation via regulating miR-218 in 16HBE cells. Biochem Biophys Res Commun. 2020 Jan 8;521(2):368–374. 10.1016/j.bbrc.2019.10.135
25. Şerifoğlu İ, Ulubay G. The methods other than spirometry in the early diagnosis of COPD. Tuberk Toraks. 2019 Mar;67(1):63–70. 10.5578/tt.68162
26. Prasad S, Kaisar MA, Cucullo L. Unhealthy smokers: scopes for prophylactic intervention and clinical treatment. BMC Neurosci. 2017 Oct 4;18(1):70. 10.1186/s12868-017-0388-6
27. Zhang S, Chen H, Wang A, Liu Y, Hou H, Hu Q. Genotoxicity analysis of five particle matter toxicants from cigarette smoke based on γH2AX assay combined with Hill/Two-component model. Environ Toxicol Pharmacol. 2018 Mar;58:131–140. 10.1016/j.etap.2018.01.003
28. Polverino F, Doyle-Eisele M, McDonald J, Wilder JA, Royer C, Laucho-Contreras M, et al. A novel nonhuman primate model of cigarette smoke-induced airway disease. Am J Pathol. 2015 Mar;185(3):741–755. 10.1016/j.ajpath.2014.11.006
29. Jasper AE, Sapey E, Thickett DR, Scott A. Understanding potential mechanisms of harm: the drivers of electronic cigarette-induced changes in alveolar macrophages, neutrophils, and lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2021 Aug 1;321(2):L336–L348. 10.1152/ajplung.00081.2021
30. Ahmad A, Ahsan H. Biomarkers of inflammation and oxidative stress in ophthalmic disorders. J Immunoassay Immunochem. 2020 May 3;41(3):257–271. 10.1080/15321819.2020.1726774
31. Vermot A, Petit-Härtlein I, Smith SME, Fieschi F. NADPH oxidases (NOX): an overview from discovery, molecular mechanisms to physiology and pathology. Antioxidants (Basel, Switzerland). 2021 Jun 1;10(6):890. 10.3390/antiox10060890
32. Fukai T, Ushio-Fukai M. Cross-Talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells. 2020 Aug 6;9(8):1849. 10.3390/cells9081849
33. Simpson DSA, Oliver PL. ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants (Basel, Switzerland). 2020 Aug 13;9(8):743. 10.3390/antiox9080743
34. Sunda F, Arowolo A. A molecular basis for the anti-inflammatory and anti-fibrosis properties of cannabidiol. FASEB J. 2020 Nov;34(11):14083–14092. 10.1096/fj.202000975R
35. Liu JQ, Zhang L, Yao J, Yao S, Yuan T. AMPK alleviates endoplasmic reticulum stress by inducing the ER-chaperone ORP150 via FOXO1 to protect human bronchial cells from apoptosis. Biochem Biophys Res Commun. 2018 Mar 4;497(2):564–570. 10.1016/j.bbrc.2018.02.095
36. Lee J, Jung HM, Kim SK, Yoo KH, Jung KS, Lee SH, et al. Factors associated with chronic obstructive pulmonary disease exacerbation, based on big data analysis. Sci Rep. 2019 Apr 30;9(1):6679. 10.1038/s41598-019-43167-w
2. Raju SV, Kim H, Byzek SA, Tang LP, Trombley JE, Jackson P, et al. A ferret model of COPD-related chronic bronchitis. JCI Insight. 2016 Sep 22;1(15):e87536. 10.1172/jci.insight.87536
3. Zhang J, Xu Q, Sun W, Zhou X, Fu D, Mao L. New insights into the role of NLRP3 inflammasome in pathogenesis and treatment of chronic obstructive pulmonary disease. J Inflam Res. 2021;14:4155–4168. 10.2147/JIR.S324323
4. Dransfield MT, Kunisaki KM, Strand MJ, Anzueto A, Bhatt SP, Bowler RP, et al. Acute exacerbations and lung function loss in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017 Feb 1;195(3):324–330.
5. Wang J, Li Y, Zhao P, Tian Y, Liu X, He H, et al. Exposure to air pollution exacerbates inflammation in rats with preexisting COPD. Mediat Inflam. 2020;2020:4260204. 10.1155/2020/4260204
6. Yamada H, Hida N, Masuko H, Sakamoto T, Hizawa N. Effects of lung function-related genes and TSLP on COPD phenotypes. Copd. 2020 Feb;17(1):59–64. 10.1080/15412555.2019.1708296
7. Cipollina C, Bruno A, Fasola S, Cristaldi M, Patella B, Inguanta R, et al. Cellular and molecular signatures of oxidative stress in bronchial epithelial cell models injured by cigarette smoke extract. Int J Mol Sci. 2022 Feb 4;23(3):1770. 10.3390/ijms23031770
8. Bodas M, Van Westphal C, Carpenter-Thompson R, Mohanty DK, Vij N. Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment. Free Radic Biol Med. 2016 Aug;97:441–453. 10.1016/j.freeradbiomed.2016.06.017
9. Dang X, He B, Ning Q, Liu Y, Guo J, Niu G, et al. Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways. Respir Res. 2020 Apr 22;21(1):95. 10.1186/s12931-020-01358-4
10. Guan R, Wang J, Cai Z, Li Z, Wang L, Li Y, et al. Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway. Redox Biol. 2020 Jan;28:101356. 10.1016/j.redox.2019.101356
11. Fernández-Hernando C, Suárez Y. ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis. Curr Opin Hematol. 2020 May;27(3):206–213. 10.1097/MOH.0000000000000580
12. Yang J, Li X, Xu D. Research progress on the involvement of ANGPTL4 and loss-of-function variants in lipid metabolism and coronary heart disease: is the “prime time” of ANGPTL4-targeted therapy for coronary heart disease approaching? Cardiovasc Drugs Therapy. 2021 Jun;35(3):467–477. 10.1007/s10557-020-07001-0
13. Aryal B, Price NL, Suarez Y, Fernández-Hernando C. ANGPTL4 in metabolic and cardiovascular disease. Trends Mol Med. 2019 Aug;25(8):723–734. 10.1016/j.molmed.2019.05.010
14. Alex S, Lange K, Amolo T, Grinstead JS, Haakonsson AK, Szalowska E, et al. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol Cell Biol. 2013 Apr;33(7):1303–1316. 10.1128/MCB.00858-12
15. Yang X, Cheng Y, Su G. A review of the multifunctionality of angiopoietin-like 4 in eye disease. Biosci Rep. 2018 Oct 31;38(5):BSR20180557. 10.1042/BSR20180557
16. Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, et al. Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing. J Biol Chem. 2010 Oct 22;285(43):32999–33009. 10.1074/jbc.M110.108175
17. Ruscica M, Zimetti F, Adorni MP, Sirtori CR, Lupo MG, Ferri N. Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia. Pharmacol Res. 2020 Mar;153:104653. 10.1016/j.phrs.2020.104653
18. Oteng AB, Ruppert PMM, Boutens L, Dijk W, van Dierendonck X, Olivecrona G, et al. Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice. J Lipid Res. 2019 Oct;60(10):1741–1754. 10.1194/jlr.M094128
19. Raschke S, Eckel J. Adipo-myokines: two sides of the same coin—mediators of inflammation and mediators of exercise. Mediat Inflam. 2013;2013:320724. 10.1155/2013/320724
20. Kang YT, Li CT, Tang SC, Hsin IL, Lai YC, Hsiao YP, et al. Nickel chloride regulates ANGPTL4 via the HIF-1α-mediated TET1 expression in lung cells. Toxicol Lett. 2021 Nov 1;352:17–25. 10.1016/j.toxlet.2021.09.007
21. Saito M, Mitani A, Ishimori T, Miyashita N, Isago H, Mikami Y, et al. Active mTOR in lung epithelium promotes epithelial-mesenchymal transition and enhances lung fibrosis. Am J Respir Cell Mol Biol. 2020 Jun;62(6):699–708. 10.1165/rcmb.2019-0255OC
22. Waschki B, Kirsten AM, Holz O, Meyer T, Lichtinghagen R, Rabe KF, et al. Angiopoietin-like protein 4 and cardiovascular function in COPD. BMJ Open Respir Res. 2016;3(1):e000161. 10.1136/bmjresp-2016-000161
23. Li L, Foo BJW, Kwok KW, Sakamoto N, Mukae H, Izumikawa K, et al. Antibody treatment against angiopoietin-like 4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia. mBio. 2019 Jun 4;10(3):e02469. 10.1128/mBio.02469-18
24. Song B, Ye L, Wu S, Jing Z. Long non-coding RNA MEG3 regulates CSE-induced apoptosis and inflammation via regulating miR-218 in 16HBE cells. Biochem Biophys Res Commun. 2020 Jan 8;521(2):368–374. 10.1016/j.bbrc.2019.10.135
25. Şerifoğlu İ, Ulubay G. The methods other than spirometry in the early diagnosis of COPD. Tuberk Toraks. 2019 Mar;67(1):63–70. 10.5578/tt.68162
26. Prasad S, Kaisar MA, Cucullo L. Unhealthy smokers: scopes for prophylactic intervention and clinical treatment. BMC Neurosci. 2017 Oct 4;18(1):70. 10.1186/s12868-017-0388-6
27. Zhang S, Chen H, Wang A, Liu Y, Hou H, Hu Q. Genotoxicity analysis of five particle matter toxicants from cigarette smoke based on γH2AX assay combined with Hill/Two-component model. Environ Toxicol Pharmacol. 2018 Mar;58:131–140. 10.1016/j.etap.2018.01.003
28. Polverino F, Doyle-Eisele M, McDonald J, Wilder JA, Royer C, Laucho-Contreras M, et al. A novel nonhuman primate model of cigarette smoke-induced airway disease. Am J Pathol. 2015 Mar;185(3):741–755. 10.1016/j.ajpath.2014.11.006
29. Jasper AE, Sapey E, Thickett DR, Scott A. Understanding potential mechanisms of harm: the drivers of electronic cigarette-induced changes in alveolar macrophages, neutrophils, and lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2021 Aug 1;321(2):L336–L348. 10.1152/ajplung.00081.2021
30. Ahmad A, Ahsan H. Biomarkers of inflammation and oxidative stress in ophthalmic disorders. J Immunoassay Immunochem. 2020 May 3;41(3):257–271. 10.1080/15321819.2020.1726774
31. Vermot A, Petit-Härtlein I, Smith SME, Fieschi F. NADPH oxidases (NOX): an overview from discovery, molecular mechanisms to physiology and pathology. Antioxidants (Basel, Switzerland). 2021 Jun 1;10(6):890. 10.3390/antiox10060890
32. Fukai T, Ushio-Fukai M. Cross-Talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells. 2020 Aug 6;9(8):1849. 10.3390/cells9081849
33. Simpson DSA, Oliver PL. ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants (Basel, Switzerland). 2020 Aug 13;9(8):743. 10.3390/antiox9080743
34. Sunda F, Arowolo A. A molecular basis for the anti-inflammatory and anti-fibrosis properties of cannabidiol. FASEB J. 2020 Nov;34(11):14083–14092. 10.1096/fj.202000975R
35. Liu JQ, Zhang L, Yao J, Yao S, Yuan T. AMPK alleviates endoplasmic reticulum stress by inducing the ER-chaperone ORP150 via FOXO1 to protect human bronchial cells from apoptosis. Biochem Biophys Res Commun. 2018 Mar 4;497(2):564–570. 10.1016/j.bbrc.2018.02.095
36. Lee J, Jung HM, Kim SK, Yoo KH, Jung KS, Lee SH, et al. Factors associated with chronic obstructive pulmonary disease exacerbation, based on big data analysis. Sci Rep. 2019 Apr 30;9(1):6679. 10.1038/s41598-019-43167-w
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Sep 1, 2022
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Liu, H., Wang, X.- xia, & Chen, P. (2022). Angiopoietin-like 4 knockdown attenuates cigarette smoke extract–induced oxidative stress and apoptosis in lung bronchial epithelial cells by inhibiting NADPH oxidase. Allergologia Et Immunopathologia, 50(5), 47-56. https://doi.org/10.15586/aei.v50i5.637
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How to Cite
Liu, H., Wang, X.- xia, & Chen, P. (2022). Angiopoietin-like 4 knockdown attenuates cigarette smoke extract–induced oxidative stress and apoptosis in lung bronchial epithelial cells by inhibiting NADPH oxidase. Allergologia Et Immunopathologia, 50(5), 47-56. https://doi.org/10.15586/aei.v50i5.637