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Titolo:
Promoter competitors as novel antifibrotics that inhibit transforming growth factor-beta induction of collagen and noncollagen protein synthesis in fibroblasts
Autore:
Meisler, NT; Chiu, JF; Cutroneo, KR;
Indirizzi:
Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA Univ Vermont Burlington VT USA 05405 pt Biochem, Burlington, VT 05405 USA
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
fascicolo: 2, volume: 75, anno: 1999,
pagine: 196 - 205
SICI:
0730-2312(19991101)75:2<196:PCANAT>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN IMMUNODEFICIENCY VIRUS; RAT LUNG FIBROBLASTS; ANTISENSE OLIGODEOXYNUCLEOTIDES; MAMMALIAN-CELLS; MESSENGER-RNA; CHLORAMPHENICOL ACETYLTRANSFERASE; PHOSPHOROTHIOATE ANALOGS; GENE-EXPRESSION; BLEOMYCIN; DEXAMETHASONE;
Keywords:
phosphorothioate oligodeoxynucleotide; promoter competitor; antifibrotic agent; collagen synthesis; collagen gene expression; fibroblast; transforming growth factor-beta 1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Cutroneo, KR Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA Univ Vermont Burlington VT USA 05405 urlington, VT 05405 USA
Citazione:
N.T. Meisler et al., "Promoter competitors as novel antifibrotics that inhibit transforming growth factor-beta induction of collagen and noncollagen protein synthesis in fibroblasts", J CELL BIOC, 75(2), 1999, pp. 196-205

Abstract

A single-stranded 27-mer phosphorothioate oligodeoxynucleotide (ssPT) containing the transforming growth factor-beta (TGF-beta) response element was synthesized. Rat fetal lung fibroblasts were stably transfected with the ColCat 3.6 plasmid, which contains a portion of the 5'-flanking region of thepro alpha 1(l) collagen gene linked to the chloramphenicol acetyltransferase (CAT) gene. The cells were transiently transfected with the modified oligodcoxynucleotides in both the presence and absence of bleomycin, a fibrogenic antineoplastic agent. At 50 mu g ssPT, the bleomycin-induced increase in CAT activity was abrogated. The ability of ssPT to inhibit collagen synthesis in rat fetal lung fibroblasts was determined. Single-stranded PTs inhibited both collagen synthesis and noncollagen protein synthesis induced by TGF-beta 1, the mediator of the bleomycin fibrogenic effect. Inflamed granulation tissue fibroblasts were prepared from polyvinyl alcohol sponges implanted in the backs of rats. These fibroblasts were treated with various doses of ssPTs in the presence and absence of TGF-beta 1. Single-stranded PTs also blocked both the TGF-beta 1-induced increase in collagen synthesis andnoncollagen synthesis in these fibroblasts. However, the TGF-beta 1-induced increase in collagen and noncollagen protein synthesis was not blocked byssPTs containing a mutated TGF-beta response element. In addition, ssPT did not significantly alter the basal levels of collagen and noncollagen protein synthesis in rat lung fibroblasts or in granuloma derived fibroblasts. Since dexamethasone was also able to block the TGF-beta 1-induced increase in collagen and noncollagen protein synthesis (Meisler et al., [1997] J. Invest. Dermatol. 108:285-289), these data indicate that phosphorothioate oligodeoxynucleotide antifibrotic agents mimic the inhibitory effect of glucocorticoids on collagen synthesis without the untoward side effects of these steroids. J. Cell. Biochem. 75:196-205, 1999. Published 1999 Wiley-Liss, Inc.dagger.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 11:49:23