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Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells

BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) mediates gene expression in response to numerous growth factors and cytokines, playing an important role in many cellular processes. To better understand the molecular mechanisms by which Stat3 influences gene expression in t...

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Autores principales: Xu, Yan, Ikegami, Machiko, Wang, Yanhua, Matsuzaki, Yohei, Whitsett, Jeffrey A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234434/
https://www.ncbi.nlm.nih.gov/pubmed/18070348
http://dx.doi.org/10.1186/1471-2164-8-455
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author Xu, Yan
Ikegami, Machiko
Wang, Yanhua
Matsuzaki, Yohei
Whitsett, Jeffrey A
author_facet Xu, Yan
Ikegami, Machiko
Wang, Yanhua
Matsuzaki, Yohei
Whitsett, Jeffrey A
author_sort Xu, Yan
collection PubMed
description BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) mediates gene expression in response to numerous growth factors and cytokines, playing an important role in many cellular processes. To better understand the molecular mechanisms by which Stat3 influences gene expression in the lung, the effect of pulmonary epithelial cell specific deletion of Stat3 on genome wide mRNA expression profiling was assessed. Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification, promoter analysis, pathway mapping and literature mining. RESULTS: Total of 791 mRNAs were significantly increased and 314 mRNAs were decreased in response to the deletion of Stat3(Δ/Δ )in the lung. STAT is the most enriched cis-elements in the promoter regions of those differentially expressed genes. Deletion of Stat3 induced genes influencing protein metabolism, transport, chemotaxis and apoptosis and decreased the expression of genes mediating lipid synthesis and metabolism. Expression of Srebf1 and 2, genes encoding key regulators of fatty acid and steroid biosynthesis, was decreased in type II cells from the Stat3(Δ/Δ )mice, consistent with the observation that lung surfactant phospholipids content was decreased. Stat3 influenced both pro- and anti-apoptotic pathways that determine cell death or survival. Akt, a potential transcriptional target of Stat3, was identified as an important participant in Stat3 mediated pathways including Jak-Stat signaling, apoptosis, Mapk signaling, cholesterol and fatty acid biosynthesis. CONCLUSION: Deletion of Stat3 from type II epithelial cells altered the expression of genes regulating diverse cellular processes, including cell growth, apoptosis and lipid metabolism. Pathway analysis indicates that STAT3 regulates cellular homeostasis through a complex regulatory network that likely enhances alveolar epithelial cell survival and surfactant/lipid synthesis, necessary for the protection of the lung during injury.
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spelling pubmed-22344342008-02-08 Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells Xu, Yan Ikegami, Machiko Wang, Yanhua Matsuzaki, Yohei Whitsett, Jeffrey A BMC Genomics Research Article BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) mediates gene expression in response to numerous growth factors and cytokines, playing an important role in many cellular processes. To better understand the molecular mechanisms by which Stat3 influences gene expression in the lung, the effect of pulmonary epithelial cell specific deletion of Stat3 on genome wide mRNA expression profiling was assessed. Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification, promoter analysis, pathway mapping and literature mining. RESULTS: Total of 791 mRNAs were significantly increased and 314 mRNAs were decreased in response to the deletion of Stat3(Δ/Δ )in the lung. STAT is the most enriched cis-elements in the promoter regions of those differentially expressed genes. Deletion of Stat3 induced genes influencing protein metabolism, transport, chemotaxis and apoptosis and decreased the expression of genes mediating lipid synthesis and metabolism. Expression of Srebf1 and 2, genes encoding key regulators of fatty acid and steroid biosynthesis, was decreased in type II cells from the Stat3(Δ/Δ )mice, consistent with the observation that lung surfactant phospholipids content was decreased. Stat3 influenced both pro- and anti-apoptotic pathways that determine cell death or survival. Akt, a potential transcriptional target of Stat3, was identified as an important participant in Stat3 mediated pathways including Jak-Stat signaling, apoptosis, Mapk signaling, cholesterol and fatty acid biosynthesis. CONCLUSION: Deletion of Stat3 from type II epithelial cells altered the expression of genes regulating diverse cellular processes, including cell growth, apoptosis and lipid metabolism. Pathway analysis indicates that STAT3 regulates cellular homeostasis through a complex regulatory network that likely enhances alveolar epithelial cell survival and surfactant/lipid synthesis, necessary for the protection of the lung during injury. BioMed Central 2007-12-10 /pmc/articles/PMC2234434/ /pubmed/18070348 http://dx.doi.org/10.1186/1471-2164-8-455 Text en Copyright © 2007 Xu 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 Article
Xu, Yan
Ikegami, Machiko
Wang, Yanhua
Matsuzaki, Yohei
Whitsett, Jeffrey A
Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells
title Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells
title_full Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells
title_fullStr Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells
title_full_unstemmed Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells
title_short Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells
title_sort gene expression and biological processes influenced by deletion of stat3 in pulmonary type ii epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234434/
https://www.ncbi.nlm.nih.gov/pubmed/18070348
http://dx.doi.org/10.1186/1471-2164-8-455
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