Polymorphisms of the TGF-?1 Promoter in Tight Skin (TSK) Mice

Publisher Website
Google Scholar
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.