Molecular aspects of regulation of collagen gene expression in fibrosis

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

Research output: Contribution to journalReview article

64 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)592-603
Number of pages12
JournalJournal of Clinical Immunology
Volume25
Issue number6
DOIs
StatePublished - Nov 1 2005

Fingerprint

Gene Expression Regulation
Interleukin-4
Fibrosis
Collagen
Interleukin-13
Fibroblasts
Cytokines
Interleukin-4 Receptors
Collagen Type III
Collagen Type I
Genes
Cicatrix

Keywords

  • Collagen
  • Fibroblasts
  • Fibrosis
  • Pro-fibrogenic cytokines
  • Scleroderma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Molecular aspects of regulation of collagen gene expression in fibrosis. / Bhogal, Rashpal K.; Stoica, Cristina M.; McGaha, Tracy L.; Bona, Constantin A.

In: Journal of Clinical Immunology, Vol. 25, No. 6, 01.11.2005, p. 592-603.

Research output: Contribution to journalReview article

Bhogal, Rashpal K. ; Stoica, Cristina M. ; McGaha, Tracy L. ; Bona, Constantin A. / Molecular aspects of regulation of collagen gene expression in fibrosis. In: Journal of Clinical Immunology. 2005 ; Vol. 25, No. 6. pp. 592-603.
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