Serum-stimulated α1 type IV collagen gene transcription is mediated by TGF-β and inhibited by estradiol

Jun Lei, Sharon Silbiger, Fuad N. Ziyadeh, Joel Neugarten

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell α1 type IV collagen (COL4A1) gene transcription by increasing autocrine production of transforming growth factor-β (TGF-β) through a platelet-derived growth factor (PDGF)-dependent mechanism. PDGF- stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-β (119.3 ± 3.6 vs. 106.0 ± 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 ± 4.1 vs. 136.7 ± 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-β (148.3 ± 4.1 vs. 127.1 ± 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-β antibody on gene transcription was no greater than that of anti- TGF-β antibody alone [129.5 ± 0.53 vs. 127.1 ± 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10-7 M) (148.4 ± 3.1 vs. 119.4 ± 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-β antibody failed to further reduce serum-stimulated gene transcription (119.4 ± 8.1 vs. 115.6 ± 9.8, P = NS), suggesting that estradiol reverses FCS- stimulated COL4A1 gene transcription by antagonizing the actions of TGF-β. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume274
Issue number2 43-2
StatePublished - Feb 1998

Fingerprint

Transforming Growth Factors
Collagen Type I
Estradiol
Luciferases
Platelet-Derived Growth Factor
Serum
Genes
Neutralizing Antibodies
Antibodies
Mesangial Cells
Collagen Type IV
Western Blotting

Keywords

  • Estrogen
  • Mesangial cells
  • Mesangial matrix
  • Sex hormones
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Serum-stimulated α1 type IV collagen gene transcription is mediated by TGF-β and inhibited by estradiol. / Lei, Jun; Silbiger, Sharon; Ziyadeh, Fuad N.; Neugarten, Joel.

In: American Journal of Physiology - Renal Physiology, Vol. 274, No. 2 43-2, 02.1998.

Research output: Contribution to journalArticle

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abstract = "We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell α1 type IV collagen (COL4A1) gene transcription by increasing autocrine production of transforming growth factor-β (TGF-β) through a platelet-derived growth factor (PDGF)-dependent mechanism. PDGF- stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-β (119.3 ± 3.6 vs. 106.0 ± 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 ± 4.1 vs. 136.7 ± 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-β (148.3 ± 4.1 vs. 127.1 ± 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-β antibody on gene transcription was no greater than that of anti- TGF-β antibody alone [129.5 ± 0.53 vs. 127.1 ± 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10-7 M) (148.4 ± 3.1 vs. 119.4 ± 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-β antibody failed to further reduce serum-stimulated gene transcription (119.4 ± 8.1 vs. 115.6 ± 9.8, P = NS), suggesting that estradiol reverses FCS- stimulated COL4A1 gene transcription by antagonizing the actions of TGF-β. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.",
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