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 language | English (US) |
|---|---|
| Pages (from-to) | 51-55 |
| Number of pages | 5 |
| Journal | Autoimmunity |
| Volume | 37 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2004 |
| Externally published | Yes |
Funding
This work was supported by grant PO1 AI24671-14 from NIAID-NIH and the Seleroderma Foundation.
Keywords
- Polymorphisms
- Promoter
- Scleroderma
- TGF-β1
- Tight skin mice
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
