Trichostatin A blocks TGF-β-induced collagen gene expression in skin fibroblasts: Involvement of Sp1

Asish K Ghosh*, Yasuji Mori, Elizabeth Dowling, John Varga

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Transforming growth factor- β (TGF-β) stimulates Type I collagen synthesis by fibroblasts and is implicated in tissue fibrosis. Here, we demonstrate that histone deacetylase inhibitor Trichostatin A (TSA) suppresses the TGF-β-induced Type I collagen synthesis but not induced PAI-1 synthesis suggesting the influence of TSA is gene specific. Results further reveal that there is no significant alteration in Smad activation and function in presence of TSA suggesting suppression of TGF-β-induced collagen synthesis is not due to impaired Smad signaling. TGF-β induces the levels of Sp1, an essential transcription factor of Smad-dependent stimulation of collagen synthesis. However, in presence of TSA, TGF-β fails to induce Sp1 levels, its interaction with Smad complex and Sp1 binding site in COL1A2 promoter. Furthermore, overexpressed Sp1 reverses the TSA-mediated inhibition of TGF-β-induced collagen gene expression. Collectively, these results suggest that TSA-mediated suppression of Smad-dependent TGF-β-induced collagen synthesis is due to suppression of Sp1 activity in skin fibroblasts.

Original languageEnglish (US)
Pages (from-to)420-426
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume354
Issue number2
DOIs
StatePublished - Mar 9 2007

Fingerprint

trichostatin A
Transforming Growth Factors
Fibroblasts
Gene expression
Skin
Collagen
Gene Expression
Collagen Type I
Sp1 Transcription Factor
Histone Deacetylase Inhibitors
Plasminogen Activator Inhibitor 1
Fibrosis
Transcription Factors
Genes
Chemical activation
Binding Sites
Tissue

Keywords

  • Fibroblasts
  • Fibrosis
  • Histone acetyltransferase
  • Histone deacetylase
  • Smad
  • Sp1
  • TGF-β
  • Trichostatin A
  • Type I collagen

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Trichostatin A blocks TGF-β-induced collagen gene expression in skin fibroblasts: Involvement of Sp1",
abstract = "Transforming growth factor- β (TGF-β) stimulates Type I collagen synthesis by fibroblasts and is implicated in tissue fibrosis. Here, we demonstrate that histone deacetylase inhibitor Trichostatin A (TSA) suppresses the TGF-β-induced Type I collagen synthesis but not induced PAI-1 synthesis suggesting the influence of TSA is gene specific. Results further reveal that there is no significant alteration in Smad activation and function in presence of TSA suggesting suppression of TGF-β-induced collagen synthesis is not due to impaired Smad signaling. TGF-β induces the levels of Sp1, an essential transcription factor of Smad-dependent stimulation of collagen synthesis. However, in presence of TSA, TGF-β fails to induce Sp1 levels, its interaction with Smad complex and Sp1 binding site in COL1A2 promoter. Furthermore, overexpressed Sp1 reverses the TSA-mediated inhibition of TGF-β-induced collagen gene expression. Collectively, these results suggest that TSA-mediated suppression of Smad-dependent TGF-β-induced collagen synthesis is due to suppression of Sp1 activity in skin fibroblasts.",
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Trichostatin A blocks TGF-β-induced collagen gene expression in skin fibroblasts : Involvement of Sp1. / Ghosh, Asish K; Mori, Yasuji; Dowling, Elizabeth; Varga, John.

In: Biochemical and Biophysical Research Communications, Vol. 354, No. 2, 09.03.2007, p. 420-426.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Mori, Yasuji

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AB - Transforming growth factor- β (TGF-β) stimulates Type I collagen synthesis by fibroblasts and is implicated in tissue fibrosis. Here, we demonstrate that histone deacetylase inhibitor Trichostatin A (TSA) suppresses the TGF-β-induced Type I collagen synthesis but not induced PAI-1 synthesis suggesting the influence of TSA is gene specific. Results further reveal that there is no significant alteration in Smad activation and function in presence of TSA suggesting suppression of TGF-β-induced collagen synthesis is not due to impaired Smad signaling. TGF-β induces the levels of Sp1, an essential transcription factor of Smad-dependent stimulation of collagen synthesis. However, in presence of TSA, TGF-β fails to induce Sp1 levels, its interaction with Smad complex and Sp1 binding site in COL1A2 promoter. Furthermore, overexpressed Sp1 reverses the TSA-mediated inhibition of TGF-β-induced collagen gene expression. Collectively, these results suggest that TSA-mediated suppression of Smad-dependent TGF-β-induced collagen synthesis is due to suppression of Sp1 activity in skin fibroblasts.

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