The relation between age and airway epithelial barrier function

Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	de Vries, M. [verfasserIn] Nwozor, K. O. Muizer, K. Wisman, M. Timens, W. van den Berge, M. Faiz, A. Hackett, T.-L. Heijink, I. H. Brandsma, C. A.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Ageing Epithelial barrier function Airway epithelial cells Chronic airway diseases

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Respiratory research - London : BioMed Central, 2001, 23(2022), 1 vom: 03. März
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:1 ; day:03 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s12931-022-01961-7

Katalog-ID:	SPR050525999

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520			\|a Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease.
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allfields	10.1186/s12931-022-01961-7 doi (DE-627)SPR050525999 (SPR)s12931-022-01961-7-e DE-627 ger DE-627 rakwb eng de Vries, M. verfasserin (orcid)0000-0001-7210-8174 aut The relation between age and airway epithelial barrier function 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. Ageing (dpeaa)DE-He213 Epithelial barrier function (dpeaa)DE-He213 Airway epithelial cells (dpeaa)DE-He213 Chronic airway diseases (dpeaa)DE-He213 Nwozor, K. O. aut Muizer, K. aut Wisman, M. aut Timens, W. aut van den Berge, M. aut Faiz, A. aut Hackett, T.-L. aut Heijink, I. H. aut Brandsma, C. A. aut Enthalten in Respiratory research London : BioMed Central, 2001 23(2022), 1 vom: 03. März (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:23 year:2022 number:1 day:03 month:03 https://dx.doi.org/10.1186/s12931-022-01961-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 03 03
spelling	10.1186/s12931-022-01961-7 doi (DE-627)SPR050525999 (SPR)s12931-022-01961-7-e DE-627 ger DE-627 rakwb eng de Vries, M. verfasserin (orcid)0000-0001-7210-8174 aut The relation between age and airway epithelial barrier function 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. Ageing (dpeaa)DE-He213 Epithelial barrier function (dpeaa)DE-He213 Airway epithelial cells (dpeaa)DE-He213 Chronic airway diseases (dpeaa)DE-He213 Nwozor, K. O. aut Muizer, K. aut Wisman, M. aut Timens, W. aut van den Berge, M. aut Faiz, A. aut Hackett, T.-L. aut Heijink, I. H. aut Brandsma, C. A. aut Enthalten in Respiratory research London : BioMed Central, 2001 23(2022), 1 vom: 03. März (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:23 year:2022 number:1 day:03 month:03 https://dx.doi.org/10.1186/s12931-022-01961-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 03 03
allfields_unstemmed	10.1186/s12931-022-01961-7 doi (DE-627)SPR050525999 (SPR)s12931-022-01961-7-e DE-627 ger DE-627 rakwb eng de Vries, M. verfasserin (orcid)0000-0001-7210-8174 aut The relation between age and airway epithelial barrier function 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. Ageing (dpeaa)DE-He213 Epithelial barrier function (dpeaa)DE-He213 Airway epithelial cells (dpeaa)DE-He213 Chronic airway diseases (dpeaa)DE-He213 Nwozor, K. O. aut Muizer, K. aut Wisman, M. aut Timens, W. aut van den Berge, M. aut Faiz, A. aut Hackett, T.-L. aut Heijink, I. H. aut Brandsma, C. A. aut Enthalten in Respiratory research London : BioMed Central, 2001 23(2022), 1 vom: 03. März (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:23 year:2022 number:1 day:03 month:03 https://dx.doi.org/10.1186/s12931-022-01961-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 03 03
allfieldsGer	10.1186/s12931-022-01961-7 doi (DE-627)SPR050525999 (SPR)s12931-022-01961-7-e DE-627 ger DE-627 rakwb eng de Vries, M. verfasserin (orcid)0000-0001-7210-8174 aut The relation between age and airway epithelial barrier function 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. Ageing (dpeaa)DE-He213 Epithelial barrier function (dpeaa)DE-He213 Airway epithelial cells (dpeaa)DE-He213 Chronic airway diseases (dpeaa)DE-He213 Nwozor, K. O. aut Muizer, K. aut Wisman, M. aut Timens, W. aut van den Berge, M. aut Faiz, A. aut Hackett, T.-L. aut Heijink, I. H. aut Brandsma, C. A. aut Enthalten in Respiratory research London : BioMed Central, 2001 23(2022), 1 vom: 03. März (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:23 year:2022 number:1 day:03 month:03 https://dx.doi.org/10.1186/s12931-022-01961-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 03 03
allfieldsSound	10.1186/s12931-022-01961-7 doi (DE-627)SPR050525999 (SPR)s12931-022-01961-7-e DE-627 ger DE-627 rakwb eng de Vries, M. verfasserin (orcid)0000-0001-7210-8174 aut The relation between age and airway epithelial barrier function 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. Ageing (dpeaa)DE-He213 Epithelial barrier function (dpeaa)DE-He213 Airway epithelial cells (dpeaa)DE-He213 Chronic airway diseases (dpeaa)DE-He213 Nwozor, K. O. aut Muizer, K. aut Wisman, M. aut Timens, W. aut van den Berge, M. aut Faiz, A. aut Hackett, T.-L. aut Heijink, I. H. aut Brandsma, C. A. aut Enthalten in Respiratory research London : BioMed Central, 2001 23(2022), 1 vom: 03. März (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:23 year:2022 number:1 day:03 month:03 https://dx.doi.org/10.1186/s12931-022-01961-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 03 03
language	English
source	Enthalten in Respiratory research 23(2022), 1 vom: 03. März volume:23 year:2022 number:1 day:03 month:03
sourceStr	Enthalten in Respiratory research 23(2022), 1 vom: 03. März volume:23 year:2022 number:1 day:03 month:03
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Ageing Epithelial barrier function Airway epithelial cells Chronic airway diseases
isfreeaccess_bool	true
container_title	Respiratory research
authorswithroles_txt_mv	de Vries, M. @@aut@@ Nwozor, K. O. @@aut@@ Muizer, K. @@aut@@ Wisman, M. @@aut@@ Timens, W. @@aut@@ van den Berge, M. @@aut@@ Faiz, A. @@aut@@ Hackett, T.-L. @@aut@@ Heijink, I. H. @@aut@@ Brandsma, C. A. @@aut@@
publishDateDaySort_date	2022-03-03T00:00:00Z
hierarchy_top_id	326646485
id	SPR050525999
language_de	englisch
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We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. 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author	de Vries, M.
spellingShingle	de Vries, M. misc Ageing misc Epithelial barrier function misc Airway epithelial cells misc Chronic airway diseases The relation between age and airway epithelial barrier function
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topic_title	The relation between age and airway epithelial barrier function Ageing (dpeaa)DE-He213 Epithelial barrier function (dpeaa)DE-He213 Airway epithelial cells (dpeaa)DE-He213 Chronic airway diseases (dpeaa)DE-He213
topic	misc Ageing misc Epithelial barrier function misc Airway epithelial cells misc Chronic airway diseases
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title	The relation between age and airway epithelial barrier function
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title_full	The relation between age and airway epithelial barrier function
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author_browse	de Vries, M. Nwozor, K. O. Muizer, K. Wisman, M. Timens, W. van den Berge, M. Faiz, A. Hackett, T.-L. Heijink, I. H. Brandsma, C. A.
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title_sort	relation between age and airway epithelial barrier function
title_auth	The relation between age and airway epithelial barrier function
abstract	Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. © The Author(s) 2022
abstractGer	Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. © The Author(s) 2022
abstract_unstemmed	Background The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing. Aim To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium. Methods We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively. Results In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells. Conclusion The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease. © The Author(s) 2022
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title_short	The relation between age and airway epithelial barrier function
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author2	Nwozor, K. O. Muizer, K. Wisman, M. Timens, W. van den Berge, M. Faiz, A. Hackett, T.-L. Heijink, I. H. Brandsma, C. A.
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The relation between age and airway epithelial barrier function

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