Angiotensin II-induced growth of vascular smooth muscle cells requires an Src-dependent activation of the epidermal growth factor receptor

Bokemeyer, Dirk; Schmitz, Udo K.; Kramer, Herbert J.

doi:10.1046/j.1523-1755.2000.t01-1-00201.x

Cited by 121 publications

(76 citation statements)

References 27 publications

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“…Early in 2001, EI Mabrouk et al demonstrated that ERK1/2 phosphorylation is dose dependently increased by Ang II in VSMCs from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats, and the ERK1/2 inhibitor PD-98059 can block Ang IIinduced VSMC growth [21] . In VSMCs, Ang II type I receptorinduced ERK1/2 activation occurs via Ca 2+ and Src-dependent transactivation of the EGFR [33,34] . Ang II can activate ERK1/2 by the Ras/PKCzeta/MEK pathway in VSMC [35] .…”

Section: Discussionmentioning

confidence: 99%

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Tong

Zhang

et al. 2010

Acta Pharmacol Sin

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Aim:To explore the effect of neferine on angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. Methods: Human umbilical vein smooth muscle cells (HUVSMCs) were used. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. Heme oxygenase (HO)-1 protein expression was tested by Western blot analysis. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation was determined by using immunoblotting. Results: Pre-incubation of HUVSMCs with neferine (0.1, 0.5, 1.0, and 5.0 µmol/L) significantly inhibited Ang II-induced cell proliferation in a concentration-dependent manner and neferine 5.0 µmol/L increased HO-1 expression by 259% compared with control. The antiproliferative effect of neferine was significantly attenuated by coapplication of zinc protoporphyrin IX (ZnPP IX, an HO-1 inhibitor) with neferine. Ang II-enhanced ERK1/2 phosphorylation was markedly reversed by neferine. By inhibiting HO-1 activity with ZnPP IX, the inhibitive effect of neferine on ERK1/2 phosphorylation was significantly attenuated. Cobalt-protoporphyrin (CoPP), an HO-1 inducer, significantly decreased Ang II-induced ERK1/2 phosphorylation and inhibited Ang II-induced cell proliferation. The ERK1/2 pathway inhibitor PD98059 significantly blocked Ang II-enhanced ERK1/2 phosphorylation and inhibited cell proliferation. Conclusion: These findings suggest that neferine can inhibit Ang II-induced HUVSMC proliferation by upregulating HO-1, leading to the at least partial downregulation of ERK1/2 phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Tong

Zhang

et al. 2010

Acta Pharmacol Sin

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“…These findings with Ang II were surprising in light of data from cultured VSMCs isolated from large arteries, which indicated an important role of EGFR transactivation in Ang II-induced ERK1/2 signaling and growth. 28 Several groups have demonstrated that EGFR transactivation is mediated by membrane shedding of HB-EGF, 20,29 and in mesangial cells, Ang II-induced HB-EGF shedding and EGFR transactivation was blocked by the MMP inhibitor batimastat. 30 Recently, Hao et al 18 have shown by use of large mesenteric arteries that ␣ 1b -adrenoreceptor-induced contraction involved MMP-7 and EGFR transactivation.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Metalloproteinases 2/9 in Epidermal Growth Factor Receptor Transactivation in Pressure-Induced Myogenic Tone in Mouse Mesenteric Resistance Arteries

et al. 2004

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Background-Epidermal growth factor receptor (EGFR) transactivation is a mediator of angiotensin II (Ang II) signaling in cultured vascular smooth muscle cells isolated from large arteries. The present study used mouse mesenteric resistance arteries (MRAs) to investigate the role of EGFR transactivation under pressure-induced myogenic tone (MT). Methods and Results-Isolated MRAs were mounted in an arteriograph and stimulated by 25 to 125 mm Hg or with Ang II and KCl. Stepwise increases in pressure resulted in MT development associated with increased EGFR phosphorylation and release of heparin-binding EGF (HB-EGF), a membrane-bound growth factor that is shed on cleavage by metalloproteinases. EGF (50 ng/mL) potentiated MT (59Ϯ1% to 51Ϯ0.6% of passive diameter at 75 mm Hg). Pretreatment with the EGFR inhibitors AG1478 (5 mol/L) or PD153035 (1 mol/L) significantly decreased MT. However, EGFR inhibitors had no effect on Ang II-and KCl-induced contraction. MT was potentiated by HB-EGF, 50 ng/mL, which is bound to the cell membrane and released on cleavage by metalloproteinases. Neutralizing HB-EGF antibodies or heparin treatment to sequester HB-EGF resulted in significant inhibition of pressure-induced MT. MT increased matrix metalloproteinase (MMP) 2 and MMP-9 gelatinase activity assessed by zymography, and specific MMP 2/9 inhibitors significantly decreased MT. Conclusions-These novel findings suggest that the mechanism of pressure-induced MT involves metalloproteinases 2/9 activation with subsequent HB-EGF release and EGFR transactivation.

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“…Several GPCR agonists stimulate EGF-R transactivation, including lysophosphatidic acid, thrombin (2,25), ANG II (14,37), arginine vasopressin (19), and ET-1 (10). More recently, a novel mechanism of EGF-R transactivation has been proposed whereby GPCR-mediated activation of Src, PYK2, and Ca 2ϩ mobilization leads to a metalloprotease proteolytic cleavage of the pro-heparinbinding (HB)-EGF precursor to yield the release of a mature ligand, which in turn activates the EGF-R (9, 32).…”

mentioning

confidence: 99%

Endothelin-1 activates mesangial cell ERK1/2 via EGF-receptor transactivation and caveolin-1 interaction

Hua

Munk

Whiteside

2003

American Journal of Physiology-Renal Physiology

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Hua, Hong, Snezana Munk, and Catharine I. Whiteside. Endothelin-1 activates mesangial cell ERK1/2 via EGFreceptor transactivation and caveolin-1 interaction. Am J Physiol Renal Physiol 284: F303-F312, 2003. First published September 17, 2002 10.1152/ajprenal.00127.2002.-Endothelin-1 (ET-1) stimulates glomerular mesangial cell proliferation and extracellular matrix protein transcription through an ERK1/2-dependent pathway. In this study, we determined whether ET-1 activation of glomerular mesangial cell ERK1/2 is mediated through EGF receptor (EGF-R) transactivation and whether intact caveolae are required. We showed that ET-1 stimulated tyrosine phosphorylation of the EGF-R in primary cultured, growth-arrested rat mesangial cells. In response to ET-1, ERK1/2 phosphorylation was increased by 27 Ϯ 1-fold and attenuated by AG-1478, a specific EGF-R inhibitor, to 9 Ϯ 1-fold. Moreover, filipin III and ␤-cyclodextrin, two cholesterol-depleting drugs known to disrupt caveolae, significantly reduced ET-1-induced phosphorylation of ERK1/2. In addition, preincubation of mesangial cells with a myristoylated peptide that binds to the caveolin-1 scaffolding domain diminished ET-1 activation of ERK1/2. ET-1 caused interaction of caveolin-1 with phosphorylated ERK1/2 identified by coimmunoprecipitation. Activation of ERK1/2 and its interaction with caveolin-1 were reduced by AG-1478, ␤-cyclodextrin, or inhibition of PKC. Phosphorylated ERK1/2 localized at focal adhesion complexes along with phospho-caveolin-1, suggesting specific sites of compartmentalization of these signaling molecules. Hence, ET-1 activates mesangial cell ERK1/2 predominantly through a pathway involving EGF-R transactivation, leading to a mechanism involving attachment to caveolin-1, presumably in caveolae.caveolae; epidermal growth factor receptor transactivation

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Angiotensin II-induced growth of vascular smooth muscle cells requires an Src-dependent activation of the epidermal growth factor receptor

Cited by 121 publications

References 27 publications

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

Involvement of Metalloproteinases 2/9 in Epidermal Growth Factor Receptor Transactivation in Pressure-Induced Myogenic Tone in Mouse Mesenteric Resistance Arteries

Endothelin-1 activates mesangial cell ERK1/2 via EGF-receptor transactivation and caveolin-1 interaction

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