title: Downregulation of ERRα inhibits angiogenesis in human umbilical vein endothelial cells through regulating VEGF production and PI3K/Akt/STAT3 signaling pathway.
abstract: The human estrogen related receptor α (ERRα) is a pivotal regulator involved in energy homeostasis and mitochondrial biogenesis. It has been demonstrated that activation of ERRα in various breast cancer cells results in a significant increase of vascular endothelial growth factor (VEGF) mRNA and protein secretion. However, little is known about the relationship between ERRα and angiogenesis. Thus, the present study is aimed to investigate the effects and mechanism of ERRα suppression on the angiogenesis in human umbilical vein endothelial cells (HUVECs). Here we show that ERRα suppression powerfully inhibits proliferation, migration and capillary-like structures formation of HUVECs. Importantly, we demonstrate that these inhibitory effects are associated with the significantly reduced expression and production of VEGF. Results from further experiments using western blot and luciferase reporter assay exhibit that ERRα suppression inhibits hypoxia-inducible factor 1α (HIF-1α) expression, and phosphorylation of protein kinase B (Akt) and signal transducer and activator of transcription (STAT3) which up-regulated VEGF expression. In summary, we show that ERRα suppression inhibits angiogenesis in HUVECs and deserves further studies for application of rationale therapeutic target for patient with diseases related with aberrant angiogenesis.
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China; Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China.
authors.forename: Liu-Di
authors.initials: LD
authors.lastname: Zhang
authors.affiliation: Pharmacy Department, Xuhui District Central Hospital, 966 Huai Hai M Road, Shanghai 200031, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Brunswick Laboratories (China), 5 Xing Han Road, Suzhou Industrial Park 215021, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Qi
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China.
authors.forename: Hai-Fei
authors.initials: HF
authors.lastname: Chen
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China; Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China.
authors.forename: Ming-Kang
authors.initials: MK
authors.lastname: Zhong
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China; Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China. Electronic address: xiaojin_shi@hotmail.com.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: Shi
authors.affiliation: Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China; Clinical Pharmacy Laboratory, Huashan Hospital North, Fudan University, 108 Luxiang Road, Shanghai 201907, China. Electronic address: qyli_sh@163.com.
authors.forename: Qun-Yi
authors.initials: QY
authors.lastname: Li
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097983:ERRalpha Estrogen-Related Receptor; C497442:HIF1A protein, human; C486497:PPARGC1A protein, human
keywords: Angiogenesis; Estrogen related receptor α; Human umbilical vein endothelial cells; Migration; Tube formation; VEGF