RESUMO
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.
Assuntos
Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana/citologia , Neovascularização Fisiológica , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Movimento Celular , Proliferação de Células , Embrião de Galinha , Membrana Corioalantoide/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional , Fator A de Crescimento do Endotélio Vascular/genética , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
BACKGROUND: To evaluate the effectiveness of the minimally traumatic midface lift approach in combination with the Wrinkle Severity Rating Scale (WSRS) criteria. METHODS: From July 2007 to September 2009, 21 female patients underwent the minimal incision midface lift procedure. The procedure was mainly composed of a small arrow-like incision just superior to the top of the auricle, a fanlike subcutaneous dissection, and 3 suspension sutures. After 6 months, objective and subjective criteria were recorded, photos were taken for documentation and the WSRS scale system was used. Postoperative adverse effects were also recorded. RESULTS: All 21 patients completed more than a 6-month postoperative follow-up, and all the patients gained complete recovery. In the doctor's evaluation for using the WSRS system, 3 patients (14.3%) felt fair, the remaining 18 patients (85.7%) felt good, and no patients (0%) had poor results 6 months after the operation. In patient self-evaluation, 5 patients (23.8%) felt fair, the remaining 16 (76.2%) felt good, and no patient (0%) had poor results after 6 months. No serious operative complications including facial nerve palsy and skin slough were found. CONCLUSION: The minimally traumatic midface lift is a simple, reliable, and effective approach for the aging face of women in their 30s and 40s.