Research article summary (published 30 Aug 2009):

Transforming growth factor-beta1 up-regulation of human alpha(1)(I) collagen is mediated by Sp1 and Smad2 transacting factors.

Full Abstract

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.

Author information

Author/s: Sysa, Polina (P); Potter, James J (JJ); Liu, Xiaopu (X); Mezey, Esteban (E);

Affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.

Grants: 2 T32 AA07467 (Agency:NIAAA NIH HHS) ; 2464388 (Agency:PHS HHS) ; AA000626 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: DNA and cell biology (DNA Cell Biol), published in United States. (Language: eng)

Reference: 2009-Sep; vol 28 (issue 9) : pp 425-34

Dates: Created 2009/08/27; Completed 2009/09/16;

PMID: 19558215, status: MEDLINE (last retrieval date: 9/16/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Base Sequence Binding Sites - genetics Blotting, Western Cell Line Chromatin Immunoprecipitation Collagen Type I - genetics Electrophoretic Mobility Shift Assay Fibroblasts - cytology; drug effects; metabolism Hepatic Stellate Cells - cytology; drug effects; metabolism Humans Mice

Mice, Knockout Mutation Promoter Regions, Genetic - genetics Protein Binding RNA, Small Interfering - genetics Smad2 Protein - genetics; metabolism Smad3 Protein - genetics; metabolism Smad4 Protein - genetics; metabolism Sp1 Transcription Factor - genetics; metabolism Transfection Transforming Growth Factor beta1 - pharmacology Up-Regulation - drug effects

Associated Chemicals: Collagen Type I (0) ; RNA, Small Interfering (0) ; Smad2 Protein (0) ; Smad3 Protein (0) ; Smad4 Protein (0) ; Sp1 Transcription Factor (0) ; Transforming Growth Factor beta1 (0) ; collagen type I, alpha 1 chain (0)

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