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 |
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Keywords
- Connective tissue growth factor
- Prenylation
- Protein kinase C
- Signaling
- Transforming growth factor-β
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Signaling events required for transforming growth factor-β stimulation of connective tissue growth factor expression by cultured human lung fibroblasts. / Kucich, U.; Rosenbloom, J. C.; Herrick, D. J.; Abrams, W. R.; Hamilton, Andrew; Sebti, S. M.; Rosenbloom, J.
In: Archives of Biochemistry and Biophysics, Vol. 395, No. 1, 01.11.2001, p. 103-112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Signaling events required for transforming growth factor-β stimulation of connective tissue growth factor expression by cultured human lung fibroblasts
AU - Kucich, U.
AU - Rosenbloom, J. C.
AU - Herrick, D. J.
AU - Abrams, W. R.
AU - Hamilton, Andrew
AU - Sebti, S. M.
AU - Rosenbloom, J.
PY - 2001/11/1
Y1 - 2001/11/1
N2 - 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.
AB - 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.
KW - Connective tissue growth factor
KW - Prenylation
KW - Protein kinase C
KW - Signaling
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=0035498841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035498841&partnerID=8YFLogxK
U2 - 10.1006/abbi.2001.2571
DO - 10.1006/abbi.2001.2571
M3 - Article
C2 - 11673871
AN - SCOPUS:0035498841
VL - 395
SP - 103
EP - 112
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 1
ER -