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Büttner, Cordula; Skupin, Annett; Rieber, Ernst Peter

Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin‐4: Analysis of the functional collagen promoter sequences

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  • Media type: E-Article
  • Title: Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin‐4: Analysis of the functional collagen promoter sequences
  • Contributor: Büttner, Cordula; Skupin, Annett; Rieber, Ernst Peter
  • imprint: Wiley, 2004
  • Published in: Journal of Cellular Physiology
  • Language: English
  • DOI: 10.1002/jcp.10395
  • ISSN: 0021-9541; 1097-4652
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Pneumonitis followed by lung fibrosis is a frequent complication of radiation therapy of chest tumors. A hallmark of these fibrotic lesions is the excessive production and accumulation of extracellular matrix proteins such as type I collagen. In addition to TGF‐β1, IL‐4 has been recognized as a potent inducer of collagen gene synthesis in fibroblasts. In this study, we analyzed the regulation of the α1(I) procollagen (<jats:italic>COL1A1</jats:italic>) promoter and the α2(I) procollagen (<jats:italic>COL1A2</jats:italic>) promoter by IL‐4 in normal human lung fibroblasts. We provide evidence that the IL‐4‐induced transcriptional activator STAT6 binds to various sequences within the <jats:italic>COL1A1</jats:italic> and <jats:italic>COL1A2</jats:italic> promoter. The regulatory function of these regions was tested by reporter gene analysis using 5′ deletions of the <jats:italic>COL1A1</jats:italic> and <jats:italic>COL1A2</jats:italic> promoter fused to the luciferase gene. Interleukin‐4 treatment of human fibroblasts transiently transfected with <jats:italic>COL1A1</jats:italic> promoter deletion constructs resulted in luciferase activity exceeding that of untreated fibroblasts by 25%, while luciferase activity driven by the <jats:italic>COL1A2</jats:italic> promoter was enhanced by about 70% upon IL‐4 treatment. A combined action of SP1, NFκB, and STAT6 essentially contributes to the IL‐4 mediated <jats:italic>COL1A2</jats:italic> gene activation. An AP2 site adjacent to the reverse orientated STAT6 consensus motif TTC <jats:italic>N</jats:italic><jats:sub>3/4</jats:sub> GCT is located within 205 bases from the transcription start site and seems to support the moderate IL‐4‐induced <jats:italic>COL1A1</jats:italic> gene activation. Interferon‐γ downregulation of transcription is mainly seen with the <jats:italic>COL1A1</jats:italic> promoter. J. Cell. Physiol. 198: 248–258, 2004© 2003 Wiley‐Liss, Inc.</jats:p>