Central role of cellular senescence in TSLP-induced airway remodeling in asthma.
BACKGROUND:Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3805661?pdf=render |
| _version_ | 1818324301477052416 |
|---|---|
| author | Jinxiang Wu Fangzheng Dong Rui-An Wang Junfei Wang Jiping Zhao Mengmeng Yang Wenbin Gong Rutao Cui Liang Dong |
| author_facet | Jinxiang Wu Fangzheng Dong Rui-An Wang Junfei Wang Jiping Zhao Mengmeng Yang Wenbin Gong Rutao Cui Liang Dong |
| author_sort | Jinxiang Wu |
| collection | DOAJ |
| description | BACKGROUND:Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma. OBJECTIVES:To examine the role of TSLP-induced cellular senescence in airway remodeling of asthma in vitro and in vivo. METHODS:Cellular senescence and airway remodeling were examined in lung specimens from patients with asthma using immunohischemical analysis. Both small molecule and shRNA approaches that target the senescent signaling pathways were used to explore the role of cellular senescence in TSLP-induced airway remodeling in vitro. Senescence-Associated β-galactosidase (SA-β-Gal) staining, and BrdU assays were used to detect cellular senescence. In addition, the Stat3-targeted inhibitor, WP1066, was evaluated in an asthma mouse model to determine if inhibiting cellular senescence influences airway remodeling in asthma. RESULTS:Activation of cellular senescence as evidenced by checkpoint activation and cell cycle arrest was detected in airway epithelia samples from patients with asthma. Furthermore, TSLP-induced cellular senescence was required for airway remodeling in vitro. In addition, a mouse asthma model indicates that inhibiting cellular senescence blocks airway remodeling and relieves airway resistance. CONCLUSION:TSLP stimulation can induce cellular senescence during airway remodeling in asthma. Inhibiting the signaling pathways of cellular senescence overcomes TSLP-induced airway remodeling. |
| first_indexed | 2024-12-13T11:26:25Z |
| format | Article |
| id | doaj.art-8b346c35ce5d4684ac023ea70a21e6ac |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T11:26:25Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8b346c35ce5d4684ac023ea70a21e6ac2022-12-21T23:48:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7779510.1371/journal.pone.0077795Central role of cellular senescence in TSLP-induced airway remodeling in asthma.Jinxiang WuFangzheng DongRui-An WangJunfei WangJiping ZhaoMengmeng YangWenbin GongRutao CuiLiang DongBACKGROUND:Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma. OBJECTIVES:To examine the role of TSLP-induced cellular senescence in airway remodeling of asthma in vitro and in vivo. METHODS:Cellular senescence and airway remodeling were examined in lung specimens from patients with asthma using immunohischemical analysis. Both small molecule and shRNA approaches that target the senescent signaling pathways were used to explore the role of cellular senescence in TSLP-induced airway remodeling in vitro. Senescence-Associated β-galactosidase (SA-β-Gal) staining, and BrdU assays were used to detect cellular senescence. In addition, the Stat3-targeted inhibitor, WP1066, was evaluated in an asthma mouse model to determine if inhibiting cellular senescence influences airway remodeling in asthma. RESULTS:Activation of cellular senescence as evidenced by checkpoint activation and cell cycle arrest was detected in airway epithelia samples from patients with asthma. Furthermore, TSLP-induced cellular senescence was required for airway remodeling in vitro. In addition, a mouse asthma model indicates that inhibiting cellular senescence blocks airway remodeling and relieves airway resistance. CONCLUSION:TSLP stimulation can induce cellular senescence during airway remodeling in asthma. Inhibiting the signaling pathways of cellular senescence overcomes TSLP-induced airway remodeling.http://europepmc.org/articles/PMC3805661?pdf=render |
| spellingShingle | Jinxiang Wu Fangzheng Dong Rui-An Wang Junfei Wang Jiping Zhao Mengmeng Yang Wenbin Gong Rutao Cui Liang Dong Central role of cellular senescence in TSLP-induced airway remodeling in asthma. PLoS ONE |
| title | Central role of cellular senescence in TSLP-induced airway remodeling in asthma. |
| title_full | Central role of cellular senescence in TSLP-induced airway remodeling in asthma. |
| title_fullStr | Central role of cellular senescence in TSLP-induced airway remodeling in asthma. |
| title_full_unstemmed | Central role of cellular senescence in TSLP-induced airway remodeling in asthma. |
| title_short | Central role of cellular senescence in TSLP-induced airway remodeling in asthma. |
| title_sort | central role of cellular senescence in tslp induced airway remodeling in asthma |
| url | http://europepmc.org/articles/PMC3805661?pdf=render |
| work_keys_str_mv | AT jinxiangwu centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT fangzhengdong centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT ruianwang centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT junfeiwang centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT jipingzhao centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT mengmengyang centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT wenbingong centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT rutaocui centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma AT liangdong centralroleofcellularsenescenceintslpinducedairwayremodelinginasthma |