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A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression

BACKGROUND: "Phosphatase and tensin homolog deleted on chromosome 10" (PTEN) is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone...

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Autores principales: Ni, ZhenHua, Tang, JiHong, Cai, ZhuYing, Yang, Wei, Zhang, Lei, Chen, Qingge, Zhang, Long, Wang, XiongBiao
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096598/
https://www.ncbi.nlm.nih.gov/pubmed/21489309
http://dx.doi.org/10.1186/1465-9921-12-47
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author Ni, ZhenHua
Tang, JiHong
Cai, ZhuYing
Yang, Wei
Zhang, Lei
Chen, Qingge
Zhang, Long
Wang, XiongBiao
author_facet Ni, ZhenHua
Tang, JiHong
Cai, ZhuYing
Yang, Wei
Zhang, Lei
Chen, Qingge
Zhang, Long
Wang, XiongBiao
author_sort Ni, ZhenHua
collection PubMed
description BACKGROUND: "Phosphatase and tensin homolog deleted on chromosome 10" (PTEN) is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation. METHODS: OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation in vitro. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone. RESULTS: PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT) by anacardic acid attenuated dexamethasone-induced PTEN expression. CONCLUSIONS: Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The in vitro studies also suggest that the PTEN pathway may be involved in human asthma.
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spelling pubmed-30965982011-05-18 A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression Ni, ZhenHua Tang, JiHong Cai, ZhuYing Yang, Wei Zhang, Lei Chen, Qingge Zhang, Long Wang, XiongBiao Respir Res Research BACKGROUND: "Phosphatase and tensin homolog deleted on chromosome 10" (PTEN) is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation. METHODS: OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation in vitro. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone. RESULTS: PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT) by anacardic acid attenuated dexamethasone-induced PTEN expression. CONCLUSIONS: Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The in vitro studies also suggest that the PTEN pathway may be involved in human asthma. BioMed Central 2011 2011-04-14 /pmc/articles/PMC3096598/ /pubmed/21489309 http://dx.doi.org/10.1186/1465-9921-12-47 Text en Copyright ©2011 Ni et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ni, ZhenHua
Tang, JiHong
Cai, ZhuYing
Yang, Wei
Zhang, Lei
Chen, Qingge
Zhang, Long
Wang, XiongBiao
A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression
title A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression
title_full A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression
title_fullStr A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression
title_full_unstemmed A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression
title_short A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression
title_sort new pathway of glucocorticoid action for asthma treatment through the regulation of pten expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096598/
https://www.ncbi.nlm.nih.gov/pubmed/21489309
http://dx.doi.org/10.1186/1465-9921-12-47
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