Open AccessTransforming Growth Factor-β1 Up-Regulation of Human α1(I) Collagen Is Mediated by Sp1 and Smad2 Transacting Factors
Author(s) -
Polina Sysa,
James J. Potter,
Xiaopu Liu,
Esteban Mezey
Publication year - 2009
Publication title -
dna and cell biology
Language(s) - English
Resource type - Journals
eISSN - 1557-7430
pISSN - 1044-5498
DOI - 10.1089/dna.2009.0884
Subject(s) - smad , biology , smad2 protein , transfection , promoter , transforming growth factor , sp1 transcription factor , microbiology and biotechnology , transforming growth factor beta , hepatic stellate cell , transcription factor , cell culture , gene , endocrinology , genetics , gene expression
Hepatic fibrosis results from excessive deposition of type I collagen. The roles of Smads in mediating the effect of transforming growth factor-beta1 (TGFbeta1) on activation of the alpha(1)(I) collagen promoter were determined. Smads bind in association with Sp1 to the CC(GG)-rich TGFbeta1 responsive element of the promoter that lacks the classical Smad recognition element, and enhance binding of Sp1. In transfection experiments, TGFbeta1 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 TGFbeta1 in enhancing the promoter. In conclusion, this study shows that Smads bind in association with Sp1 to the CC(GG)-rich TGFbeta1 responsive element of the human alpha(1)(I) collagen promoter that lacks the classical Smad recognition element, thus enhancing the binding of Sp1 and in this manner activating the collagen promoter.