Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling
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 a...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/4875421 |
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| author | Lingli Long Yubin Li Shuang Yu Xiang Li Yue Hu Tengfei Long Liqin Wang Wenwen Li Xiaoxin Ye Zunfu Ke Haipeng Xiao |
| author_facet | Lingli Long Yubin Li Shuang Yu Xiang Li Yue Hu Tengfei Long Liqin Wang Wenwen Li Xiaoxin Ye Zunfu Ke Haipeng Xiao |
| author_sort | Lingli Long |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a805b99f5fd849afaa81c6a9c83a934f |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-a805b99f5fd849afaa81c6a9c83a934f2025-02-03T01:30:32ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/48754214875421Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway SignalingLingli Long0Yubin Li1Shuang Yu2Xiang Li3Yue Hu4Tengfei Long5Liqin Wang6Wenwen Li7Xiaoxin Ye8Zunfu Ke9Haipeng Xiao10Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaThe Reproductive Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaTranslation Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Gynaecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaLaboratory Animal Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaUniversity of New South Wales, Sydney, High St. Kensington, NSW, AustraliaDepartment of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaBackground. 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.http://dx.doi.org/10.1155/2019/4875421 |
| spellingShingle | Lingli Long Yubin Li Shuang Yu Xiang Li Yue Hu Tengfei Long Liqin Wang Wenwen Li Xiaoxin Ye Zunfu Ke Haipeng Xiao Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling Journal of Diabetes Research |
| title | Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling |
| title_full | Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling |
| title_fullStr | Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling |
| title_full_unstemmed | Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling |
| title_short | Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling |
| title_sort | scutellarin prevents angiogenesis in diabetic retinopathy by downregulating vegf erk fak src pathway signaling |
| url | http://dx.doi.org/10.1155/2019/4875421 |
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