Polymorphisms of the TGF-β1 promoter in tight skin (TSK) mice

Hong Zhu, Constantin Bona, Tracy L. McGaha

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

TGF-β1 plays a major role in fibrotic diseases including scleroderma. Human fibroblasts from sclerotic lesions display an increased sensitivity to TGF-β1. Similarly, fibroblasts from TSK mice which develop a scleroderma-like syndrome are hyperresponsive to TGF-β. The aim of the present study was to investigate whether the TGF-β hypersensitivity demonstrated by TSK/+ fibroblasts is associated with polymorphisms of the TGF-β1 promoter. Sequence analysis revealed one polymorphism (a G → T at - 1133 bp) unique to the TSK/+ mouse. Transfection of fibroblasts with a 1.8 kb fragment of the TGF-β1 promoter containing the - 1133 polymorphism exhibited increased basal TGF-β1 promoter activity which was enhanced upon incubation with TGF-β1. This may be related to the loss of a negative regulatory site in the TSK/+ TGF-β1 promoter.

Original languageEnglish (US)
Pages (from-to)51-55
Number of pages5
JournalAutoimmunity
Volume37
Issue number1
DOIs
StatePublished - Feb 1 2004

Keywords

  • Polymorphisms
  • Promoter
  • Scleroderma
  • TGF-β1
  • Tight skin mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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