Signaling events required for transforming growth factor-β stimulation of connective tissue growth factor expression by cultured human lung fibroblasts

Umberto Kucich, Joan C. Rosenbloom, David J. Herrick, William R. Abrams, Andrew D. Hamilton, Saïd M. Sebti, Joel Rosenbloom

Research output: Contribution to journalArticle

Abstract

It is possible that many of the fibrogenic effects of transforming growth factor-β (TGF-β) are mediated by connective tissue growth factor (CTGF). In the present work, we show that TGF-β1 produces a 5- to 6-fold increase in CTGF expression by cultured human lung fibroblasts that is due mainly to increased transcription. The half-life of CTGF mRNA is 1.96 h, consistent with its role as a cytokine. In addition to requiring Smad activity, based upon the effects of specific inhibitors, the TGF-β intracellular signaling pathway requires the activity of a phosphatidylcholine-specific phospholipase C, a protein kinase C, and one or more tyrosine kinases. It is also likely that the pathway requires a member of the Ras superfamily of small GTPases, but not trimeric G proteins. Pharmacologic inhibition of TGF-β stimulation of CTGF expression may be an effective therapeutic approach to a variety of undesirable fibrotic reactions.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume395
Issue number1
DOIs
StatePublished - Nov 1 2001

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Keywords

  • Transforming growth factor-β
  • connective tissue growth factor
  • prenylation
  • protein kinase C
  • signaling

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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