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Titolo:
Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells
Autore:
Motojima, M; Ando, T; Yoshioka, T;
Indirizzi:
Kureha Chem Ind Co, Biomed Res Labs, Shinjuku Ku, Tokyo 1698503, Japan Kureha Chem Ind Co Tokyo Japan 1698503 Shinjuku Ku, Tokyo 1698503, Japan Tokyo Womens Med Univ, Sch Med, Dept Pharmacol, Shinjuku Ku, Tokyo 1628666, Japan Tokyo Womens Med Univ Tokyo Japan 1628666 njuku Ku, Tokyo 1628666, Japan
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 349, anno: 2000,
parte:, 2
pagine: 435 - 441
SICI:
0264-6021(20000715)349:<435:SAMAPI>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; TRANSCRIPTIONAL REGULATION; SP1 PHOSPHORYLATION; DNA-BINDING; IN-VIVO; MODULATION; GROWTH; SYSTEM; PLAYS;
Keywords:
double-stranded decoy oligodeoxynucleotide; extracellular matrix; transcription; plasmin system;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Motojima, M Kureha Chem Ind Co, Biomed Res Labs, Shinjuku Ku, 3-26-2 Hyakunin Cho, Tokyo 1698503, Japan Kureha Chem Ind Co 3-26-2 Hyakunin Cho TokyoJapan 1698503 an
Citazione:
M. Motojima et al., "Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells", BIOCHEM J, 349, 2000, pp. 435-441

Abstract

Angiotensin II (Ang II) up-regulates plasminogen-activator inhibitor type-1 (PAI-1) expression in mesangial cells to enhance extracellular matrix formation. The proximal promoter region (bp -87 to -45) of the human PAI-1 gene contains several potent binding sites for transcription factors [two phorbol-ester-response-element (TRE)-like sequences; D-box (-82 to -76) and P-box (-61 to 54), and one Sp1 binding site-like sequence, Sp1-box 1 (-72 to -67)]. We studied this region to determine the transcription factor(s) that mediates Ang-II-induced transcriptional activation of the PAI-1 gene. Various double-stranded decoy oligodeoxynucleotides (ODNs) corresponding to various sequences in the proximal promoter region were transfected to mesangialcells to examine the effects on Ang-II-induced PAI-L mRNA expression. Transfection with the full-length decoy (bp -87 to -45, D-P-ODN) markedly attenuated Ang-II-induced PAI-I mRNA expression by up to 70%,, Transfection withD-ODN (-87 to -71) and P-ODN (-66 to -45), which correspond to each of thetwo TRE-like sequences, did not attenuate the expression. Gel-shift assaysusing nuclear extracts prepared from Ang-II-treated mesangial cells and D-P-ODN showed three specific complexes. The major complex was supershifted by anti-Sp1 antibody. The methylation-interference experiment demonstrated that human recombinant Spl bound to the so-called GT box (TGGGTGGGGCT, -78 to -69), which contains the Sp1-box 1. The complex that migrated with anti-Spl antibody was enhanced in the cells treated with Ang II. Further, D-Sp1-ODN (-85 to -63) containing the GT box attenuated upregulation of PAI-1 mRNAexpression induced by Ang II to a level (68+/-9% inhibition) comparable toD-P-ODN, whereas ODN with four mutations in the GT box had no effect. Our findings suggest that binding of Sp1 or an Sp1-like transcription factor tothe GT box in the PAI-1 promoter up-regulates PAI-1 gene transcription in mesangial cells stimulated with Ang II. This transcription-factor binding site may be targeted to control AngII-dependent extracellular matrix formation by mesangial cells.

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Documento generato il 11/07/20 alle ore 03:24:02