Journal of Clinical Immunology

, 25:592

Molecular Aspects of Regulation of Collagen Gene Expression in Fibrosis

  • Rashpal K. Bhogal
  • Cristina M. Stoica
  • Tracy L. McGaha
  • Constantin A. Bona
Article

Abstract

Fibrosis, the hyper-accumulation of scar tissue, is characterized by the overproduction and deposition of type I and III collagen by fibroblasts and is the one of the main pathologic outcomes of the autoimmune disorder scleroderma. While the causes of fibrosis in scleroderma are unknown, cytokines such as TGF-β, IL-4 and IL-13, play a crucial role in the stimulation of collagen production have been implicated in the disease process. In fibroblasts stimulation of collagen production by these cytokines is dependent on the Smad and STAT6 signaling pathways induced by TGF-β and IL-4, IL-13 respectively. Furthermore, mounting evidence suggest cytokine crosstalk is relevant in the sclerotic process. Our laboratory demonstrated an increase in TGF-β1 gene transcription from fibroblasts stimulated with IL-4. In addition, TSK/+ mice lacking the IL-4α receptor show impaired transcription of the TGF-β1 gene and did not display fibrosis. Likewise, it appears that STAT6 plays a role in fibroblast TGF-β1 transcription after IL-4 or IL-13 stimulation. These findings suggest that an epistatic interaction between IL-4 and TGF-β may exist which is crucial for pathologic sclerotic activity.

Key Words

Fibrosis scleroderma pro-fibrogenic cytokines fibroblasts collagen 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Rashpal K. Bhogal
    • 1
  • Cristina M. Stoica
    • 1
  • Tracy L. McGaha
    • 2
  • Constantin A. Bona
    • 1
    • 3
  1. 1.Department of MicrobiologyMount Sinai School of MedicineNew York
  2. 2.Laboratory of Molecular Genetics and ImmunologyThe Rockefellar UniversityNew York
  3. 3.Department of MicrobiologyThe Mount Sinai School of MedicineNew York

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