Estrogen Receptor α Interacts with Gα13 to Drive Actin Remodeling and Endothelial Cell Migration via the RhoA/Rho Kinase/Moesin Pathway

Simoncini, Tommaso; Scorticati, Camila; Mannella, Paolo; Fadiel, Ahmed; Giretti, Maria Silvia; Fu, Xiaodong; Baldacci, Chiara; Garibaldi, Silvia; Caruso, A.; Fornari, Letizia; Naftolin, Frederick; Genazzani, Andrea Riccardo

doi:10.1210/me.2005-0259

Cited by 168 publications

(170 citation statements)

References 44 publications

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“…Previously, we and others have demonstrated that estrogen induces vasodilatation, and regulates vascular cell growth and migration as well as protects cardiomyocytes from injury (Simoncini et al 2006, Liu et al 2007, Kublickiene et al 2008. The present study reveals that estrogen exerts anti-inflammatory activity in VSMCs by reducing LPS-induced MCP-1 production, thus inhibiting cell migration.…”

Section: Discussionsupporting

confidence: 69%

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Jiang¹,

Xu²,

Zheng³

et al. 2010

Journal of Molecular Endocrinology

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Atherosclerosis is an inflammatory disease where lipopolysaccharide (LPS) triggers the release of inflammatory cytokines that accelerate its initiation and progression. Estrogen has been proven to be vasoprotective against atherosclerosis; however, the anti-inflammatory function of estrogen in the vascular system remains obscure. In this study, we investigated the effect of estrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1; listed as CCL2 in the MGI database) production in vascular smooth muscle cells (VSMCs). LPS significantly enhances MCP-1 production and this is dependent on nuclear factor k B (NFkB) signaling, since the use of NFkB inhibitor pyrrolidine dithiocarbamate or the silencing of NFkB subunit p65 expression with specific siRNA largely impairs LPS-enhanced MCP-1 production. On the contrary, 17b-estradiol (E 2 ) inhibits LPS-induced MCP-1 production in a time-and dosedependent manner, which is related to the suppression of p65 translocation to nucleus. Furthermore, p38 MAPK is rapidly activated in response to LPS, while E 2 markedly inhibits p38 MAPK activation. Transfection with p38 MAPK siRNA or the use of p38 MAPK inhibitor SB203580 markedly attenuates LPS-stimulated p65 translocation to nucleus and MCP-1 production, suggesting that E 2 suppresses NFkB signaling by the inactivation of p38 MAPK signaling. LPS promotes VSMCs migration and this is abrogated by MCP-1 antibody, implying that MCP-1 may play a major role as an autocrine factor in atherosclerosis. In addition, E 2 inhibits LPS-promoted cell migration by downregulation of MCP-1 production.Overall, our results demonstrate that E 2 exerts anti-inflammatory property antagonistic to LPS in VSMCs by reducing MCP-1 production, and this effect is related to the inhibition of p38 MAPK/NFkB cascade.

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Section: Discussionsupporting

confidence: 69%

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Jiang¹,

Xu²,

Zheng³

et al. 2010

Journal of Molecular Endocrinology

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“…The mER and caveolin in myelin partition to a low density detergent-insoluble glycosphingolipid/cholesterol-enriched fraction containing actin and tubulin (Arvanitis et al, 2005). Simoncini et al (2006) revealed a novel nongenomic function of mERa in EC, triggered by its interaction with the G protein Ga 13, resulting in remodeling of the actin cytoskeleton. Remodeling of the cytoskeleton and changes in cell morphology are important events in OL maturation and myelination processes.…”

Section: Discussionmentioning

confidence: 96%

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Hirahara

Matsuda

Gao

et al. 2008

Glia

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There is general acceptance that the estrogen receptor can act as a transcription factor. However, estrogens can also bind to receptors that are located at the plasma membrane and stimulate rapid intracellular signaling processes. We recently showed that a membrane-associated estrogen receptor (mER) is present within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the physiological function of mER in OLs, we investigated its cellular localization and involvement in rapid signaling in CG4 cells and OL primary cultures. An ERa was expressed along the lacy network of veins in the membrane sheets and in the perikaryon and nucleus in OLs. ERb was located in the nucleus, and to a lesser extent along the veins. The expression of ERa and ERb in OL membranes was confirmed by Western analysis of isolated membranes. OL membranes mainly had truncated forms of ERa, 53 and 50 kDa, in addition to some 65 kDa form, whereas ERb was a 54 kDa form. CG4 cells and OLs were pulsed with 17a-and 17b-estradiol for various times and the total lysates were analyzed for phosphorylated kinases. Both 17a-and 17b-estradiol elicited rapid phosphorylation of p42/44MAPK, Akt, and GSK-3b within 8 min. This rapid signaling is consistent with estradiol ligation of a membrane form of ER. Since 17a-estradiol is produced at higher concentrations than 17b-estradiol in the brain of both sexes, signaling via 17a-estradiol-liganded mER may have an important function in OLs. V V C

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“…Simoncini T et al [16] have detected the expression of NHERF1 in HUVECs and speculated that it might play a certain role in angiogenesis. Song GJ et al [17] found that NHERF1 is only expressed in normal vascular endothelial cells, but almost not in vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Study on Effects of NHERF-1 on Proliferation and Migration of Human Umbilical Vein Endothelial Cells

Li¹,

Chu²,

Feng³

et al. 2017

Proceedings of the 2017 7th International Conference on Applied Science, Engineering and Technology (ICASET 2017)

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Abstract.ObjectTo explore the effects of Na + /H + exchanger regulatory factor 1 (NHERF1) on the phosphorylation levels of Akt1, activity of gelatinase secreted by HUVECs, and expression and distribution of cytoskeleton inside Human Umbilical Vein Endothelial Cells (HUVECs), and to expound the molecular mechanism of NHERF1 to influence the proliferation, migration and angiogenesis of vascular endothelial cells. Methods To construct the recombinant eukaryotic expression plasmid of NHERF1 and stably transfect HUVEC line with recombinant plasmid respectively; the 3-4,5-Dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) was used to assay the proliferation activity of HUVECs after verification with the Western blotting method; to adopt the scarification test to measure the migration activity of HUVECs; to apply the Matrigel method to detect the angiogenesis ability of NHERF1 in cells; to detect the effect of NHERF1 on the phosphorylation levels of Akt1 by Western blotting; to use the gelatin zymography analysis to test the activity of gelatinase secreted by HUVECs; to observe the distribution of cytoskeleton with the immunofluorescence. Results The cDNA fragments of the exogenous NHERF-1 transfected have been integrated into the genome; NHERF-1 can significantly inhibit the proliferation, migration and angiogenesis of HUVECs, obviously down-regulate the phosphorylation levels of Akt11, make HUVECs decrease the secretion of reduction proenzyme and active enzyme, and also influence the distribution of cytoskeleton in vascular endothelial cells, compared to the cells in the control group. Conclusion NHERF1 can inhibit proliferation, migration and angiogenesis of HUVECs, and the inhibiting mechanism might relate to adjustment of the phosphorylation levels of Akt11, regulation of the activity of gelatinase secreted by HUVECs, and influence on the distribution of microfilament cytoskeleton.

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Estrogen Receptor α Interacts with Gα13 to Drive Actin Remodeling and Endothelial Cell Migration via the RhoA/Rho Kinase/Moesin Pathway

Cited by 168 publications

References 44 publications

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Study on Effects of NHERF-1 on Proliferation and Migration of Human Umbilical Vein Endothelial Cells

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