Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium
Rationale: Damage to airway epitheliumis followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the e...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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AMER THORACIC SOC
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/76818 |
| _version_ | 1848763767944380416 |
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| author | Kicic, Anthony Hallstrand, T.S. Sutanto, E.N. Stevens, P.T. Kobor, M.S. Taplin, C. Paré, P.D. Beyer, R.P. Stick, S.M. Knight, D.A. |
| author_facet | Kicic, Anthony Hallstrand, T.S. Sutanto, E.N. Stevens, P.T. Kobor, M.S. Taplin, C. Paré, P.D. Beyer, R.P. Stick, S.M. Knight, D.A. |
| author_sort | Kicic, Anthony |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Rationale: Damage to airway epitheliumis followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n = 36), healthy atopic control subjects (n = 23), and healthy nonatopic control subjects (n = 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5′, 2′ deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. |
| first_indexed | 2025-11-14T11:08:42Z |
| format | Journal Article |
| id | curtin-20.500.11937-76818 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:08:42Z |
| publishDate | 2010 |
| publisher | AMER THORACIC SOC |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-768182019-11-12T06:14:59Z Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium Kicic, Anthony Hallstrand, T.S. Sutanto, E.N. Stevens, P.T. Kobor, M.S. Taplin, C. Paré, P.D. Beyer, R.P. Stick, S.M. Knight, D.A. Science & Technology Life Sciences & Biomedicine Critical Care Medicine Respiratory System General & Internal Medicine fibronectin asthma epithelium wound repair inflammation OBSTRUCTIVE PULMONARY-DISEASE GROWTH-FACTOR RECEPTOR GENE-EXPRESSION AIRWAY EPITHELIUM INHALED CORTICOSTEROIDS BRONCHIAL EPITHELIUM IN-VIVO CELL-PROLIFERATION ALLERGEN CHALLENGE PEDIATRIC-AIRWAY Rationale: Damage to airway epitheliumis followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n = 36), healthy atopic control subjects (n = 23), and healthy nonatopic control subjects (n = 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5′, 2′ deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. 2010 Journal Article http://hdl.handle.net/20.500.11937/76818 10.1164/rccm.200907-1071OC English AMER THORACIC SOC restricted |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Critical Care Medicine Respiratory System General & Internal Medicine fibronectin asthma epithelium wound repair inflammation OBSTRUCTIVE PULMONARY-DISEASE GROWTH-FACTOR RECEPTOR GENE-EXPRESSION AIRWAY EPITHELIUM INHALED CORTICOSTEROIDS BRONCHIAL EPITHELIUM IN-VIVO CELL-PROLIFERATION ALLERGEN CHALLENGE PEDIATRIC-AIRWAY Kicic, Anthony Hallstrand, T.S. Sutanto, E.N. Stevens, P.T. Kobor, M.S. Taplin, C. Paré, P.D. Beyer, R.P. Stick, S.M. Knight, D.A. Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| title | Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| title_full | Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| title_fullStr | Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| title_full_unstemmed | Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| title_short | Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| title_sort | decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium |
| topic | Science & Technology Life Sciences & Biomedicine Critical Care Medicine Respiratory System General & Internal Medicine fibronectin asthma epithelium wound repair inflammation OBSTRUCTIVE PULMONARY-DISEASE GROWTH-FACTOR RECEPTOR GENE-EXPRESSION AIRWAY EPITHELIUM INHALED CORTICOSTEROIDS BRONCHIAL EPITHELIUM IN-VIVO CELL-PROLIFERATION ALLERGEN CHALLENGE PEDIATRIC-AIRWAY |
| url | http://hdl.handle.net/20.500.11937/76818 |