Polymorphisms of the TGF-beta1 promoter in tight skin (TSK) mice.
TGF-beta1 plays a major role in fibrotic diseases including scleroderma. Human fibroblasts from sclerotic lesions display an increased sensitivity to TGF-beta1. Similarly, fibroblasts from TSK mice which develop a scleroderma-like syndrome are hyperresponsive to TGF-beta. The aim of the present study was to investigate whether the TGF-beta hypersensitivity demonstrated by TSK/+ fibroblasts is associated with polymorphisms of the TGF-beta1 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-beta1 promoter containing the -1133 polymorphism exhibited increased basal TGF-beta1 promoter activity which was enhanced upon incubation with TGF-beta1. This may be related to the loss of a negative regulatory site in the TSK/+ TGF-beta1 promoter.
Zhu
Hong
H
Department of Microbiology, Box 1124, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Bona
Constantin
C
McGaha
Tracy L
TL
D000818:Animals; D001483:Base Sequence; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012595:Scleroderma, Systemic / Q000235:genetics; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1