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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2005-10-27
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pubmed:abstractText |
The signal transducer and activator of transcription (Stat)-1 mediates growth arrest and apoptosis. We postulated that lung fibrosis characterized by excessive proliferation of lung fibroblasts would be enhanced in Stat1-deficient (Stat1-/-) mice. Two weeks after bleomycin aspiration (3 U/kg), Stat1-/- mice exhibited a more severe fibroproliferative response and significantly elevated total lung collagen compared to wild-type mice. Growth factors [epidermal growth factor (EGF) or platelet-derived growth factor (PDGF)] enhanced [3H]thymidine uptake in lung fibroblasts isolated from Stat1-/- mice compared to wild-type mice. Interferon (IFN)-gamma, which signals growth arrest via Stat1, inhibited EGF- or PDGF-stimulated mitogenesis in wild-type fibroblasts but enhanced [3H]thymidine uptake in Stat1-/- fibroblasts. Moreover, IFN-gamma treatment in the absence of growth factors induced a concentration-dependent increase in [3H]thymidine uptake in Stat1-/- but not wild-type fibroblasts. Mitogen-activated protein kinase (ERK-1/2) phosphorylation in response to PDGF or EGF did not differ among Stat1-/- and wild-type fibroblasts. However, Stat3 phosphorylation induced by PDGF, EGF, or IFN-gamma increased twofold in Stat1-/- fibroblasts compared to wild-type fibroblasts. Our findings indicate that Stat1-/- mice are more susceptible to bleomycin-induced lung fibrosis than wild-type mice due to 1) enhanced fibroblast proliferation in response to growth factors (EGF and PDGF), 2) stimulation of fibroblast growth by a Stat1-independent IFN-gamma signaling pathway, and 3) increased activation of Stat3.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-10393853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-10528036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-10559305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-10646607,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11159045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11169589,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11171987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11261329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11325598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11390994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11390995,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11404481,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11470919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-11929133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-12444037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-12663336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-15155567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-15207816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-7518191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8556994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8607977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8608597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8608598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8621573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8755534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8770944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-8821811,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16251407-9374464
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyproline,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1221-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16251407-Animals,
pubmed-meshheading:16251407-Bleomycin,
pubmed-meshheading:16251407-Blotting, Western,
pubmed-meshheading:16251407-Cell Proliferation,
pubmed-meshheading:16251407-Cells, Cultured,
pubmed-meshheading:16251407-Collagen,
pubmed-meshheading:16251407-Disease Models, Animal,
pubmed-meshheading:16251407-Epidermal Growth Factor,
pubmed-meshheading:16251407-Fibroblasts,
pubmed-meshheading:16251407-Growth Inhibitors,
pubmed-meshheading:16251407-Hydroxyproline,
pubmed-meshheading:16251407-Interferon-gamma,
pubmed-meshheading:16251407-Lung,
pubmed-meshheading:16251407-Male,
pubmed-meshheading:16251407-Mice,
pubmed-meshheading:16251407-Mice, Knockout,
pubmed-meshheading:16251407-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:16251407-Phosphorylation,
pubmed-meshheading:16251407-Platelet-Derived Growth Factor,
pubmed-meshheading:16251407-Pulmonary Fibrosis,
pubmed-meshheading:16251407-STAT1 Transcription Factor,
pubmed-meshheading:16251407-STAT3 Transcription Factor,
pubmed-meshheading:16251407-Thymidine
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pubmed:year |
2005
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pubmed:articleTitle |
Susceptibility of signal transducer and activator of transcription-1-deficient mice to pulmonary fibrogenesis.
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pubmed:affiliation |
CIIT Centers for Health Research, P.O. Box 12137, Research Triangle Park, NC 27709, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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