Stat-3 is required for pulmonary homeostasis during hyperoxia
Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epitheli...
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| Veröffentlicht in: | The Journal of clinical investigation 2004-01, Vol.113 (1), p.28-37 |
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| container_title | The Journal of clinical investigation |
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| creator | Hokuto, Isamu Ikegami, Machiko Yoshida, Mitsuhiro Takeda, Kiyoshi Akira, Shizuo Perl, Anne-Karina T Hull, William M Wert, Susan E Whitsett, Jeffrey A |
| description | Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3-deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3-deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3-deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury. |
| doi_str_mv | 10.1172/jci19491 |
| format | Article |
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Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3-deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3-deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3-deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci19491</identifier><identifier>PMID: 14702106</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Adult ; Animals ; Apoptosis ; Base Sequence ; Biomedical research ; Child ; Cytokines ; DNA Primers ; DNA-Binding Proteins - deficiency ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Growth factors ; Histology ; Homeostasis ; Humans ; Hyperoxia ; Hypoxia - physiopathology ; Immunohistochemistry ; Kinases ; Laboratories ; Lung - pathology ; Lung - physiology ; Lung - physiopathology ; Lung Diseases - genetics ; Lung Diseases - pathology ; Lung Diseases - physiopathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Morphogenesis ; Phosphorylation ; Polymerase Chain Reaction ; Proteins ; Pulmonary Surfactant-Associated Protein B - physiology ; Respiratory distress syndrome ; Respiratory Mucosa - physiology ; RNA, Messenger - genetics ; Severe acute respiratory syndrome ; STAT3 Transcription Factor ; Surfactants ; Trans-Activators - deficiency ; Trans-Activators - genetics ; Trans-Activators - physiology ; Transcription, Genetic</subject><ispartof>The Journal of clinical investigation, 2004-01, Vol.113 (1), p.28-37</ispartof><rights>Copyright American Society for Clinical Investigation Jan 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3911-7dfe8de3c47302ca4382a1f94b18b05e978e96d2c1aafafac3946f9a57e3ff083</citedby><cites>FETCH-LOGICAL-c3911-7dfe8de3c47302ca4382a1f94b18b05e978e96d2c1aafafac3946f9a57e3ff083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14702106$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hokuto, Isamu</creatorcontrib><creatorcontrib>Ikegami, Machiko</creatorcontrib><creatorcontrib>Yoshida, Mitsuhiro</creatorcontrib><creatorcontrib>Takeda, Kiyoshi</creatorcontrib><creatorcontrib>Akira, Shizuo</creatorcontrib><creatorcontrib>Perl, Anne-Karina T</creatorcontrib><creatorcontrib>Hull, William M</creatorcontrib><creatorcontrib>Wert, Susan E</creatorcontrib><creatorcontrib>Whitsett, Jeffrey A</creatorcontrib><title>Stat-3 is required for pulmonary homeostasis during hyperoxia</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3-deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3-deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3-deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.</description><subject>Adult</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biomedical research</subject><subject>Child</subject><subject>Cytokines</subject><subject>DNA Primers</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Growth factors</subject><subject>Histology</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Hyperoxia</subject><subject>Hypoxia - physiopathology</subject><subject>Immunohistochemistry</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Lung - pathology</subject><subject>Lung - physiology</subject><subject>Lung - physiopathology</subject><subject>Lung Diseases - genetics</subject><subject>Lung Diseases - pathology</subject><subject>Lung Diseases - physiopathology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Morphogenesis</subject><subject>Phosphorylation</subject><subject>Polymerase Chain Reaction</subject><subject>Proteins</subject><subject>Pulmonary Surfactant-Associated Protein B - physiology</subject><subject>Respiratory distress syndrome</subject><subject>Respiratory Mucosa - physiology</subject><subject>RNA, Messenger - genetics</subject><subject>Severe acute respiratory syndrome</subject><subject>STAT3 Transcription Factor</subject><subject>Surfactants</subject><subject>Trans-Activators - deficiency</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - physiology</subject><subject>Transcription, Genetic</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkE1LAzEQhoMotlbBXyCLB_GymslHkxw8SPGjUvCgnpd0N7FbdjdrsgH7701tQZA5zGGeeZl5EDoHfAMgyO26rEExBQdoDJzLXBIqD9EYYwK5ElSO0EkIa4yBMc6O0QiYSCM8HaO7t0EPOc3qkHnzFWtvqsw6n_WxaV2n_SZbuda4MOiQkCr6uvvMVpveePdd61N0ZHUTzNm-T9DH48P77DlfvD7NZ_eLvKQKIBeVNbIytGSCYlJqRiXRYBVbglxibpSQRk0rUoLWNlXaYlOrNBeGWoslnaCrXW7v3Vc0YSjaOpSmaXRnXAyFxFhI4Fvw8h-4dtF36baCYMwlIYon6HoHld6F4I0tel-36dcCcLH1WbzM5r8-E3qxz4vL1lR_4F4g_QGECG9V</recordid><startdate>200401</startdate><enddate>200401</enddate><creator>Hokuto, Isamu</creator><creator>Ikegami, Machiko</creator><creator>Yoshida, Mitsuhiro</creator><creator>Takeda, Kiyoshi</creator><creator>Akira, Shizuo</creator><creator>Perl, Anne-Karina T</creator><creator>Hull, William M</creator><creator>Wert, Susan E</creator><creator>Whitsett, Jeffrey A</creator><general>American Society for Clinical Investigation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>200401</creationdate><title>Stat-3 is required for pulmonary homeostasis during hyperoxia</title><author>Hokuto, Isamu ; Ikegami, Machiko ; Yoshida, Mitsuhiro ; Takeda, Kiyoshi ; Akira, Shizuo ; Perl, Anne-Karina T ; Hull, William M ; Wert, Susan E ; Whitsett, Jeffrey A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3911-7dfe8de3c47302ca4382a1f94b18b05e978e96d2c1aafafac3946f9a57e3ff083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Biomedical research</topic><topic>Child</topic><topic>Cytokines</topic><topic>DNA Primers</topic><topic>DNA-Binding Proteins - 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Academic</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hokuto, Isamu</au><au>Ikegami, Machiko</au><au>Yoshida, Mitsuhiro</au><au>Takeda, Kiyoshi</au><au>Akira, Shizuo</au><au>Perl, Anne-Karina T</au><au>Hull, William M</au><au>Wert, Susan E</au><au>Whitsett, Jeffrey A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stat-3 is required for pulmonary homeostasis during hyperoxia</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2004-01</date><risdate>2004</risdate><volume>113</volume><issue>1</issue><spage>28</spage><epage>37</epage><pages>28-37</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3-deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3-deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3-deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>14702106</pmid><doi>10.1172/jci19491</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adult Animals Apoptosis Base Sequence Biomedical research Child Cytokines DNA Primers DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Growth factors Histology Homeostasis Humans Hyperoxia Hypoxia - physiopathology Immunohistochemistry Kinases Laboratories Lung - pathology Lung - physiology Lung - physiopathology Lung Diseases - genetics Lung Diseases - pathology Lung Diseases - physiopathology Mice Mice, Knockout Mice, Transgenic Morphogenesis Phosphorylation Polymerase Chain Reaction Proteins Pulmonary Surfactant-Associated Protein B - physiology Respiratory distress syndrome Respiratory Mucosa - physiology RNA, Messenger - genetics Severe acute respiratory syndrome STAT3 Transcription Factor Surfactants Trans-Activators - deficiency Trans-Activators - genetics Trans-Activators - physiology Transcription, Genetic |
| title | Stat-3 is required for pulmonary homeostasis during hyperoxia |
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