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Titolo:
Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation
Autore:
Fujiyama, S; Matsubara, H; Nozawa, Y; Maruyama, K; Mori, Y; Tsutsumi, Y; Masaki, H; Uchiyama, Y; Koyama, Y; Nose, A; Iba, O; Tateishi, E; Ogata, N; Jyo, N; Higashiyama, S; Iwasaka, T;
Indirizzi:
Kansai Med Univ, Dept Med 2, Osaka 5708507, Japan Kansai Med Univ Osaka Japan 5708507 iv, Dept Med 2, Osaka 5708507, Japan Kansai Med Univ, Dept Ophthalmol, Osaka 5708507, Japan Kansai Med Univ Osaka Japan 5708507 ept Ophthalmol, Osaka 5708507, Japan Taiho Pharmaceut Co Ltd, Pharmacol Lab, Tokushima, Japan Taiho Pharmaceut Co Ltd Tokushima Japan Pharmacol Lab, Tokushima, Japan Osaka Univ, Fac Med, Sch Allied Hlth Sci, Dept Biochem, Osaka, Japan OsakaUniv Osaka Japan Sch Allied Hlth Sci, Dept Biochem, Osaka, Japan
Titolo Testata:
CIRCULATION RESEARCH
fascicolo: 1, volume: 88, anno: 2001,
pagine: 22 - 29
SICI:
0009-7330(20010105)88:1<22:AAAARD>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE ACTIVATION; SMOOTH-MUSCLE CELLS; TYROSINE KINASE; POSTNATAL NEOVASCULARIZATION; TIE2 RECEPTOR; MESSENGER-RNA; UP-REGULATION; BLOOD-VESSEL; IN-VIVO; VASCULOGENESIS;
Keywords:
angiotensin II; angiopoietin; angiogenesis; vascular endothelial growth factor; endothelial cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Matsubara, H Kansai Med Univ, Dept Med 2, Fumizonocho 10-15, Osaka 5708507, Japan Kansai Med Univ Fumizonocho 10-15 Osaka Japan 5708507 Japan
Citazione:
S. Fujiyama et al., "Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation", CIRCUL RES, 88(1), 2001, pp. 22-29

Abstract

Angiotensin II (Ang II)-mediated signals are transmitted via heparin binding epidermal growth factor (EGF)-like growth factor (HB-EGF) release followed by transactivation of EGF receptor (EGFR), Although Ang II and HB-EGF induce angiogenesis, their Link to the angiopoietin (Ang)-Tie2 system remainsundefined, We tested the effects of Ang II on Ang1, Ang2, or Tie2 expression in cardiac microvascular endothelial cells expressing the Ang II receptors AT(1) and AT(2). Ang II significantly induced Ang2 mRNA accumulations without affecting Ang1 or Tie2 expression, which was inhibited by protein kinase C inhibitors and by intracellular Ca2+ chelating agents. Ang II transactivated EGFR via AT(1), and inhibition of EGFR abolished the induction of Ang2. Ang II caused processing of pro-HB-EGF in a metalloproteinase-dependent manner to stimulate maturation and release of HB-EGF, Neutralizing anti-HB-EGF antibody blocked EGFR phosphorylation by Ang II. Ang II also upregulated vascular endothelial growth factor (VEGF) expression in an HB-EGF/EGFR-dependent manner. AT(2) inhibited AT(1)-mediated Ang2, expression and phosphorylation of EGFR, In an in vivo corneal assay, AT(1) induced angiogenesisin an HB-EGF-dependent manner and enhanced the angiogenic activity of VEGF. Although neither Ang2 nor An,al alone induced angiogenesis, soluble Tie2-Fc that binds to angiopoietins attenuated AT(1)-mediated angiogenesis, These findings suggested that (1) Ang II induces Ang2 and VEGF expression without affecting Ang1 or Tie2 and (2) AT(1) stimulates processing of pro-HB-EGFby metalloproteinases, and the released HB-EGF transactivates EGFR to induce angiogenesis via the combined effect of Ang2 and VEGF, whereas AT(2) attenuates them by blocking EGFR phosphorylation, Thus, Ang II is involved in the VEGF-Ang-Tie2 system via HB-EGF-mediated EGFR transactivation, and thislink should be considerable in pathological conditions in which collateralblood flow is required.

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Documento generato il 25/09/20 alle ore 21:57:45