| The IL-6 Trans-Signaling-STAT3 Pathway Mediates ECM and Cellular Proliferation in Fibroblasts from Hypertrophic Scar. | |
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MedLine Citation:
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PMID: 23303450 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The molecular mechanisms behind the pathogenesis of postburn hypertrophic scar (HS) remain unclear. Here, we investigate the role of the IL-6 trans-signaling-signal transducer and activator of transcription (STAT)3 pathway in HS fibroblasts (HSFs) derived from post-burn HS skin. HSF showed increased Tyr 705 STAT3 phosphorylation compared with normal fibroblast (NF) after IL-6•IL-6Rα stimulation by immunoassays. The endogenous STAT3 target gene, SOCS3, was upregulated in HSFs and showed increased STAT3 binding on its promoter relative to NFs in a chromatin immunoprecipitation assay. We observed that the cell-surface signaling transducer glycoprotein 130 is upregulated in HSFs by quantitative real-time reverse-transcriptase-PCR and flow cytometry. The production of excessive extracellular matrix (ECM), including the expression of alpha2 (1) procollagen (Col1A2) and fibronectin 1 (FN), was seen in HSFs. A STAT3 peptide inhibitor abrogated FN and Col1A2 gene expression in HSFs indicating involvement of STAT3 in ECM production. The cellular proliferation markers Cyclin D1, Bcl-Xl, and c-Myc were also upregulated in HSF, and knockdown of STAT3 by small interfering RNA attenuated c-Myc expression indicating the essential role of STAT3 in fibroblast proliferation. Taken together, our results suggest that the IL-6 trans-signaling-STAT3 pathway may have an integral role in HS pathogenesis, and disruption of this pathway could be a potential therapeutic strategy for the treatment of post-burn HS.Journal of Investigative Dermatology advance online publication, 10 January 2013; doi:10.1038/jid.2012.499. |
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Authors:
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Sutapa Ray; Xiaoxi Ju; Hong Sun; Celeste C Finnerty; David N Herndon; Allan R Brasier |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-10 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: - ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department of Internal Medicine, Endocrinology Division, University of Texas Medical Branch, Galveston, Texas, USA [2] Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas, USA [3] Shriners Hospitals for Children Galveston, University of Texas Medical Branch, Galveston, Texas, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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