Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Mitogenic and antiapoptotic actions of hepatocyte growth factor through ERK, STAT3, and Akt in endothelial cells
Autore:
Nakagami, H; Morishita, R; Yamamoto, K; Taniyama, Y; Aoki, M; Matsumoto, K; Nakamura, T; Kaneda, Y; Horiuchi, M; Ogihara, T;
Indirizzi:
Osaka Univ, Grad Sch Med, Dept Geriatr Med, Osaka, Japan Osaka Univ Osaka Japan iv, Grad Sch Med, Dept Geriatr Med, Osaka, Japan Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Osaka, Japan Osaka Univ Osaka Japan Grad Sch Med, Div Gene Therapy Sci, Osaka, Japan Osaka Univ, Grad Sch Med, Biomed Res Ctr, Dept Oncol,Div Biochem, Osaka, Japan Osaka Univ Osaka Japan ed Res Ctr, Dept Oncol,Div Biochem, Osaka, Japan Ehime Univ, Sch Med, Dept Med Biochem, Matsuyama, Ehime 790, Japan Ehime Univ Matsuyama Ehime Japan 790 Biochem, Matsuyama, Ehime 790, Japan
Titolo Testata:
HYPERTENSION
fascicolo: 2, volume: 37, anno: 2001,
parte:, 2 supplemento:, S
pagine: 581 - 586
SICI:
0194-911X(200102)37:2<581:MAAAOH>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR TYROSINE KINASE; NECROSIS-FACTOR-ALPHA; SCATTER FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; ADHESION MOLECULE-1; FACTOR GENE; EXPRESSION; INHIBITOR; RESPONSES;
Keywords:
vascular; growth substances; kinase; apoptosis; transcription;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Morishita, R Osaka Univ, Sch Med, Dept Geriatr Med, 2-2 Yamadaoka, Suita, Osaka 565, Japan Osaka Univ 2-2 Yamadaoka Suita Osaka Japan 565 aka 565, Japan
Citazione:
H. Nakagami et al., "Mitogenic and antiapoptotic actions of hepatocyte growth factor through ERK, STAT3, and Akt in endothelial cells", HYPERTENSIO, 37(2), 2001, pp. 581-586

Abstract

Hepatocyte growth factor (HGF), a member of the angiogenic growth factors,may play a pivotal role in the regulation of endothelial cells, inasmuch as HGF shows mitogenic and antiapoptotic actions in endothelial cells. Because the mechanism of these actions is still unclear, we examined the signal transduction system of HGF in human aortic endothelial cells. Treatment of endothelial cells with recombinant HGF (rHGF) resulted in a significant increase in DNA synthesis as assessed by thymidine incorporation. Importantly,phosphorylation of extracellular signal-related kinase (ERK) and Akt by rHGF was clearly observed. Thus, we further examined the effects of specific inhibitors of ERK or Akt on cell proliferation. Pretreatment with PD98059, a mitogen-activated protein kinase kinase inhibitor, significantly attenuated cell proliferation induced by rHGF, whereas inhibitors of phosphatidylinositol-3-OH kinase, wortmannin, and LY-294002, did not. Interestingly, treatment with rHGF significantly increased the phosphorylation of the signal transducers and activators of transcription (STAT)3 (Ser727), whereas PD98059 attenuated the phosphorylation of Ser727 induced by rHGF, In addition, treatment with rHGF significantly increased the promoter activity of c-Sos, which includes the sis-inducible element and serum response element, whereasPD98059 completely attenuated the activation of the c-fos promoter inducedby rHGF. In contrast, inhibition of Akt by wortmannin and LY-294002 failedto inhibit the phosphorylation of STAT3 and c-fos activation. On the otherhand, treatment with rHGF attenuated the increase in LDH release and caspase-3 activity induced by tumor necrosis factor-alpha stimulation, In contrast to DNA synthesis, wortmannin and LY-294002 markedly attenuated the decrease in caspase-3 activity mediated by rHGF, whereas PD98059 did not. Overall, the present study demonstrated that HGF stimulated cell proliferation through the ERK-STAT3 (Ser727) pathway and had an antiapoptotic action through the phosphatidylinositol-3-OH kinase-Akt pathway in human aortic endothelial cells. These findings provide new perspectives in the role of HGF in cardiovascular disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 02:20:51