Transforming growth factor-β1 up-regulation of human α1(I) collagen is mediated by Sp1 and Smad2 transacting factors

Polina Sysa, James J. Potter, Xiaopu Liu, Esteban Mezey

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatic fibrosis results from excessive deposition of type I collagen. The roles of Smads in mediating the effect of transforming growth factor-β1 (TGFβ1) on activation of the α1(I) collagen promoter were determined. Smads bind in association with Sp1 to the CC(GG)-rich TGFβ1 responsive element of the promoter that lacks the classical Smad recognition element, and enhance binding of Sp1. In transfection experiments, TGFβ1 activated a proximal promoter, but not promoters mutated at sites that prevented Sp1 binding. Sp1 alone or the combination of Smad2 and Smad4 activated the promoter in transfected human LX-2 stellate cells. Sp1 or Smad2 knockdowns with siRNAs prevented the effect of TGFβ1 in enhancing the promoter. In conclusion, this study shows that Smads bind in association with Sp1 to the CC(GG)-rich TGFβ1 responsive element of the human α1(I) collagen promoter that lacks the classical Smad recognition element, thus enhancing the binding of Sp1 and in this manner activating the collagen promoter.

Original languageEnglish (US)
Pages (from-to)425-434
Number of pages10
JournalDNA and Cell Biology
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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