A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract
BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of CO...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.690936/full |
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| author | Qing Chen Qing Chen Maaike de Vries Maaike de Vries Kingsley Okechukwu Nwozor Kingsley Okechukwu Nwozor Jacobien A. Noordhoek Jacobien A. Noordhoek Jacobien A. Noordhoek Corry-Anke Brandsma Corry-Anke Brandsma H. Marike Boezen H. Marike Boezen Irene H. Heijink Irene H. Heijink Irene H. Heijink |
| author_facet | Qing Chen Qing Chen Maaike de Vries Maaike de Vries Kingsley Okechukwu Nwozor Kingsley Okechukwu Nwozor Jacobien A. Noordhoek Jacobien A. Noordhoek Jacobien A. Noordhoek Corry-Anke Brandsma Corry-Anke Brandsma H. Marike Boezen H. Marike Boezen Irene H. Heijink Irene H. Heijink Irene H. Heijink |
| author_sort | Qing Chen |
| collection | DOAJ |
| description | BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses.Materials and MethodsProtein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA.ResultsFAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels.ConclusionOur data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia. |
| first_indexed | 2024-12-17T05:08:21Z |
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| language | English |
| last_indexed | 2024-12-17T05:08:21Z |
| publishDate | 2021-06-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-e36be87b67a64c17af9479686224c2722022-12-21T22:02:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.690936690936A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke ExtractQing Chen0Qing Chen1Maaike de Vries2Maaike de Vries3Kingsley Okechukwu Nwozor4Kingsley Okechukwu Nwozor5Jacobien A. Noordhoek6Jacobien A. Noordhoek7Jacobien A. Noordhoek8Corry-Anke Brandsma9Corry-Anke Brandsma10H. Marike Boezen11H. Marike Boezen12Irene H. Heijink13Irene H. Heijink14Irene H. Heijink15Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsBackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses.Materials and MethodsProtein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA.ResultsFAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels.ConclusionOur data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia.https://www.frontiersin.org/articles/10.3389/fphys.2021.690936/fullCOPD-Chronic obstructive pulmonary diseaseFAM13Aairway epitheliumbarrier functionCXCL8 |
| spellingShingle | Qing Chen Qing Chen Maaike de Vries Maaike de Vries Kingsley Okechukwu Nwozor Kingsley Okechukwu Nwozor Jacobien A. Noordhoek Jacobien A. Noordhoek Jacobien A. Noordhoek Corry-Anke Brandsma Corry-Anke Brandsma H. Marike Boezen H. Marike Boezen Irene H. Heijink Irene H. Heijink Irene H. Heijink A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract Frontiers in Physiology COPD-Chronic obstructive pulmonary disease FAM13A airway epithelium barrier function CXCL8 |
| title | A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract |
| title_full | A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract |
| title_fullStr | A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract |
| title_full_unstemmed | A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract |
| title_short | A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract |
| title_sort | protective role of fam13a in human airway epithelial cells upon exposure to cigarette smoke extract |
| topic | COPD-Chronic obstructive pulmonary disease FAM13A airway epithelium barrier function CXCL8 |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.690936/full |
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