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Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling.
Long, Lingli; Li, Yubin; Yu, Shuang; Li, Xiang; Hu, Yue; Long, Tengfei; Wang, Liqin; Li, Wenwen; Ye, Xiaoxin; Ke, Zunfu; Xiao, Haipeng.
Afiliación
  • Long L; Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Li Y; Translation Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Yu S; The Reproductive Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Li X; Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Hu Y; Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Long T; Translation Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Wang L; Department of Gynaecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • Li W; Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Ye X; Laboratory Animal Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Ke Z; University of New South Wales, Sydney, High St. Kensington, NSW, Australia.
  • Xiao H; Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
J Diabetes Res ; 2019: 4875421, 2019.
Article en En | MEDLINE | ID: mdl-31976335
BACKGROUND: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. The antiangiogenic mechanisms of SCU in vitro and in vivo were investigated. METHOD: HRECs were cultured in high glucose- (30 mM D-glucose) and hypoxia (cobalt chloride-treated)-stimulated diabetic condition to evaluate the antiangiogenic effects of SCU by CCK-8 test, cell migration experiment (wound healing and transwell), and tube formation experiment. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. We further used western blot, luciferase reporter assay, and immunofluorescence staining to study the antiangiogenic mechanism of SCU. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats. RESULT: Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. SCU suppressed the crosstalk of phospho-ERK, phospho-FAK, phospho-Src, and VEGF in vivo and in vitro. CONCLUSIONS: These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Familia-src Quinasas / Inhibidores de la Angiogénesis / Factor A de Crecimiento Endotelial Vascular / Apigenina / Quinasas MAP Reguladas por Señal Extracelular / Retinopatía Diabética / Proteína-Tirosina Quinasas de Adhesión Focal / Glucuronatos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Diabetes Res Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Familia-src Quinasas / Inhibidores de la Angiogénesis / Factor A de Crecimiento Endotelial Vascular / Apigenina / Quinasas MAP Reguladas por Señal Extracelular / Retinopatía Diabética / Proteína-Tirosina Quinasas de Adhesión Focal / Glucuronatos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Diabetes Res Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido