Upregulated VEGF and Robo4 correlate with the reduction of miR-15a in the development of diabetic retinopathy

Autor: Qiaoyun Gong, Jia'nan Xie, Fuqiang Li, Guanfang Su
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Angiogenesis
Endocrinology
Diabetes and Metabolism
Down-Regulation
030209 endocrinology & metabolism
Receptors
Cell Surface
Retina
Rats
Sprague-Dawley
03 medical and health sciences
Tissue culture
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Vasculogenesis
Downregulation and upregulation
Diabetes mellitus
Internal medicine
medicine
Human retinal pigment epithelial cell
Animals
Humans
Cells
Cultured
miRNA
Aged
Diabetic Retinopathy
business.industry
Human retinal endothelial cell
Roundabout 4
Colocalization
Diabetic retinopathy
Middle Aged
medicine.disease
VEGF
Rats
Up-Regulation
Vascular endothelial growth factor
MicroRNAs
chemistry
030220 oncology & carcinogenesis
Disease Progression
Original Article
Female
business
Zdroj: Endocrine
ISSN: 1559-0100
1355-008X
Popis: Purpose Vascular endothelial growth factor (VEGF) plays implicated roles in diabetic retinopathy (DR). The role of roundabout 4 (Robo 4) in angiogenesis and vasculogenesis is controversial; however, the interdependent relationship between these two factors has not been studied in DR. This study determined the colocalization of VEGF and Robo4 in fibrovascular membranes (FVM) from patients with proliferative diabetic retinopathy (PDR). MicroRNA (miRNA)-mediated modulation of VEGF and Robo4 was explored in diabetic rats and ARPE-19 tissue culture cells under hyperglycemia. Methods VEGF and Robo4 co-expression in the FVM was analyzed using immunofluorescence. VEGF and Robo4 levels were determined in diabetic retinas and ARPE-19 tissue culture cells under high glucose using western blotting and RT-qPCR. MicroRNA agomir was intraocularly injected to increase miR-15a expression and downregulate VEGF and Robo4 levels in diabetic retinas. Results VEGF and Robo4 colocalization in FVM vessels was observed. Increased VEGF levels were consistent in diabetic retinas and ARPE-19 tissue culture cells cultured under hyperglycemia. Robo4 decreased in ARPE-19 tissue culture cells exposed to hyperglycemia for 72 h, whereas it increased in diabetic rat retinas. Several miRNAs were differentially expressed during DR progression. Furthermore, miR-15a agomir injection inhibited high levels of VEGF and Robo4 in diabetic retinas. Conclusions VEGF and Robo4 were co-expressed in FVMs from PDR patients. In the early stages of DR, VEGF was upregulated and contributed to DR development, whereas, in the late stage of DR, VEGF and Robo4 worked together to aggravate DR progression. However, miR-15a could downregulate VEGF and Robo4 to ameliorate DR development.
Databáze: OpenAIRE
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