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 language | English (US) |
---|---|
Pages (from-to) | 103-112 |
Number of pages | 10 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 395 |
Issue number | 1 |
DOIs | |
State | Published - Nov 1 2001 |
Keywords
- Transforming growth factor-β
- connective tissue growth factor
- prenylation
- protein kinase C
- signaling
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology