Dibutyl phthalate promotes angiogenesis in EA.hy926 cells through estrogen receptor-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways

Kokai, Dunja; Stanić, Bojana; Tesic, Biljana; Nenadov, Dragana Samardzija; Pogrmić-Majkić, Kristina; Nedeljkovic, Svetlana Fa; Andrić, Nebojša

doi:10.1016/j.cbi.2022.110174

Cited by 10 publications

(2 citation statements)

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“…The subsequent transactivation of the epidermal growth factor receptor (EGFR) can further activate the ERK1/2 signaling pathway [ 67 ]. Through this mechanism, GPER mediates vasodilation by promoting NO production [ 68 ], induces smooth muscle cell proliferation [ 69 ], and promotes angiogenesis by upregulating angiotensin [ 70 ], and protects the myocardium from ischemia/reperfusion injury by reducing mitochondrial dysfunction and mitochondrial autophagy [ 71 , 72 ]. In addition, relevant studies in lung and breast cancer have shown that the activation of the Src/ERK1/2 pathway by GPER involves the activation of mitogen-activated protein kinase kinases (MEK) [ 73 , 74 , 75 , 76 ], which is consistent with our general understanding of the mitogen-activated protein kinase (MAPK) signaling pathway.…”

Section: Tissue Cellular Localization Ligands and Classical Signaling...mentioning

confidence: 99%

“…Pollyana et al showed that the GPER-dependent relaxation of mesenteric resistance arteries is mainly mediated by the PI3K–Akt–eNOS pathway and attenuated by non-specific potassium channel block [ 165 ]. The molecular mechanism of GPER-dependent activation of the ERK1/2, PI3K-Akt, and NO signaling pathways was also supported by dibutyl phthalate (DBP)-induced endothelial cell proliferation [ 70 ]. Notably, there appear to be sex differences in the mechanistic pathways involved in eNOS phosphorylation: the PI3k–Akt–eNOS pathway was identified in males, and the MEK–ERK–eNOS pathway was validated in females [ 166 ].…”

Section: The Role Of Gper In Vascular Pathology and Physiologymentioning

confidence: 99%

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The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology

Xu,

Ma,

Wang

et al. 2023

Biomolecules

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Objective: Estrogen is indispensable in health and disease and mainly functions through its receptors. The protection of the cardiovascular system by estrogen and its receptors has been recognized for decades. Numerous studies with a focus on estrogen and its receptor system have been conducted to elucidate the underlying mechanism. Although nuclear estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been shown to be classical receptors that mediate genomic effects, studies now show that GPER mainly mediates rapid signaling events as well as transcriptional regulation via binding to estrogen as a membrane receptor. With the discovery of selective synthetic ligands for GPER and the utilization of GPER knockout mice, significant progress has been made in understanding the function of GPER. In this review, the tissue and cellular localizations, endogenous and exogenous ligands, and signaling pathways of GPER are systematically summarized in diverse physiological and diseased conditions. This article further emphasizes the role of GPER in vascular pathology and physiology, focusing on the latest research progress and evidence of GPER as a promising therapeutic target in hypertension, pulmonary hypertension, and atherosclerosis. Thus, selective regulation of GPER by its agonists and antagonists have the potential to be used in clinical practice for treating such diseases.

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