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Titolo:
Activation of a fibroblast-specific enhancer of the Pro alpha 2(I) collagen gene in tight-skin mice
Autore:
Denton, CP; Bing, Z; Xu, SW; Zhang, ZP; Bou-Gharios, G; Eberspaecher, H; Black, CM; de Crombrugghe, B;
Indirizzi:
Univ Texas, Houston, TX USA Univ Texas Houston TX USAUniv Texas, Houston, TX USA Univ Coll London, London, England Univ Coll London London EnglandUniv Coll London, London, England
Titolo Testata:
ARTHRITIS AND RHEUMATISM
fascicolo: 3, volume: 44, anno: 2001,
pagine: 712 - 722
SICI:
0004-3591(200103)44:3<712:AOAFEO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; SYSTEMIC-SCLEROSIS FIBROBLASTS; ALPHA-1(I) PROCOLLAGEN GENE; TRANSGENIC MICE; INCREASED EXPRESSION; CONNECTIVE-TISSUE; FIBRILLIN-1 GENE; REPORTER GENES; MOUSE; PROMOTER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Denton, CP Royal Free & Univ Coll Med Sch, Ctr Rheumatol, Royal Free Campus,Rowland Hill St, London NW3 2PF, England Royal Free & Univ Coll Med Sch Royal Free Campus,Rowland Hill St London England NW3 2PF
Citazione:
C.P. Denton et al., "Activation of a fibroblast-specific enhancer of the Pro alpha 2(I) collagen gene in tight-skin mice", ARTH RHEUM, 44(3), 2001, pp. 712-722

Abstract

Objective. Reporter transgenes were introduced into the type 1 tight-skin (Tsk1/+) mouse model of scleroderma to test the hypothesis that fibroblast-specific genetic programs are activated in fibrosis. Methods. Transgenes harboring upstream fragments of the 5' flanking regionof the mouse pro alpha2(I) collagen gene (Colla2), linked to a 400-bp minimal Colla2 promoter driving an Escherichia coli beta -galactosidase (LacZ) reporter gene, were introduced into Tsk1/+ mice by breeding. Expression of these transgenes, which function as lineage-specific markers of fibroblast differentiation, was compared between the Tsk-LacZ mice and non-Tsk littermates. Responsiveness of these constructs to the profibrotic cytokine, transforming growth factor beta1 (TGF beta1), was investigated by transient transfection of reporter constructs in tissue-culture cells. Results. There was significant activation of reporter genes harboring the upstream enhancer in Tsk1/+ mice starting from 1 week of age. This was maximal at 6 weeks old (mean +/- SD 237 +/- 24% of non-Tsk controls; P = 0.001). Recombinant TGF beta1 significantly activated reporter genes regulated bythe upstream enhancer in transient transfection, and Tsk-LacZ fibroblasts showed elevated LacZ expression in tissue culture. Conclusion. These data suggest that activating signals in Tsk1/+ mice may act via fibroblast-specific regulatory elements within the murine Colla2 gene. Although TGF beta has been implicated in the pathogenesis of fibrosis, and reporter genes regulated by the upstream enhancer appear to be TGF betaresponsive in vitro, our results suggest that fibroblast-specific pathwaysmay also be involved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 19:07:26