Factors involved in the regulation of type I collagen gene expression: Implication in fibrosis

Asish K. Ghosh*

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

206 Scopus citations

Abstract

Type I collagen, the major component of extracellular matrix in skin and other tissues, is a heterotrimer of two α1 and one α2 collagen polypeptides. The synthesis of both chains is highly regulated by different cytokines at the transcriptional level. Excessive synthesis and deposition of collagen in the dermal region causes thick and hard skin, a clinical manifestation of scleroderma. To better understand the causes of scleroderma or other tissue fibrosis, it is very important to investigate the molecular mechanisms that cause upregulation of the Type I collagen synthesis in these tissues. Several cis-acting regulatory elements and trans-acting protein factors, which are involved in basal as well as cytokine-modulated Type I collagen gene expression, have been identified and characterized. Hypertranscription of Type I collagen in scleroderma skin fibroblasts may be due to abnormal activities of different positive or negative transcription factors in response to different abnormally induced signaling pathways. In this review, I discuss the present day understanding about the involvement of different factors in the regulation of basal as well as cytokine-modulated Type I collagen gene expression and its implication in scleroderma research.

Original languageEnglish (US)
Pages (from-to)301-314
Number of pages14
JournalExperimental Biology and Medicine
Volume227
Issue number5
DOIs
StatePublished - May 2002

Keywords

  • Extracellular matrix
  • IFN-γ
  • IL-1β
  • Scleroderma
  • Signal transduction
  • TGF-β
  • TNF-α
  • Transcription factors
  • Transcriptional coactivators p300/CBP
  • Type I collagen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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