title: Kaempferol inhibited VEGF and PGF expression and in vitro angiogenesis of HRECs under diabetic-like environment.
abstract: Diabetic retinopathy (DR) is one of the common and specific microvascular complications of diabetes. This study aimed to investigate the anti-angiogenic effect of kaempferol and explore its underlying molecular mechanisms. The mRNA expression level of vascular endothelial growth factor (VEGF) and placenta growth factor (PGF) and the concentrations of secreted VEGF and PGF were measured by qTR-PCR and ELISA assay, respectively. Human retinal endothelial cells (HRECs) proliferation, migration, and sprouting were measured by CCK-8 and transwell, scratching wound, and tube formation assays, respectively. Protein levels were determined by western blot. High glucose (25 mM) increased the mRNA expression levels of VEGF and PGF as well as the concentrations of secreted VEGF and PGF in HRECs, which can be antagonized by kaempferol (25 µM). Kaempferol (5-25 µM) significantly suppressed cell proliferation, migration, migration distance and sprouting of HRECs under high glucose condition. The anti-angiogenic effect of kaempferol was mediated via downregulating the expression of PI3K and inhibiting the activation of Erk1/2, Src, and Akt1. This study indicates that kaempferol suppressed angiogenesis of HRECs via targeting VEGF and PGF to inhibit the activation of Src-Akt1-Erk1/2 signaling pathway. The results suggest that kaempferol may be a potential drug for better management of DR.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, Jiangsu Province, China.|People's Liberation Army 454 Hospital, Nanjing City, Jiangsu Province, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, Jiangsu Province, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.affiliation: People's Liberation Army 454 Hospital, Nanjing City, Jiangsu Province, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, Jiangsu Province, China.
authors.forename: P
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, Jiangsu Province, China.
authors.forename: Q H
authors.initials: QH
authors.lastname: Liu
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D044949:Kaempferols / Q000494:pharmacology*; D000072483:Placenta Growth Factor / Q000037:antagonists & inhibitors*; D012160:Retina / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D044949:Kaempferols; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C006552:kaempferol