Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy
| Autor: | Shi-Feng Fang, Xiuhong Qin, Xiang Ma, Jianmin Lu, Zhenzhen Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis Blotting Western Apoptosis Epigenetic Repression Transfection Diabetes Mellitus Experimental Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Phosphatidylinositol 3-Kinases VEGF Signaling Pathway PTEN Tensin Animals Viability assay Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Diabetic Retinopathy biology Neovascularization Pathologic Chemistry Reverse Transcriptase Polymerase Chain Reaction PTEN Phosphohydrolase Endothelial Cells Retinal Vessels Flow Cytometry Immunohistochemistry Sensory Systems Rats Vascular endothelial growth factor Ophthalmology MicroRNAs biology.protein Cancer research Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Experimental eye research. 190 |
| ISSN: | 1096-0007 |
| Popis: | Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the most common causes of blindness in active stage. This study is performed to explore the effects of microRNA-21 (miR-21) on retinal vascular endothelial cell (RVEC) viability and angiogenesis in rats with DR via the phosphatidylinositiol 3-kinase/protein kinase B (PI3K/Akt)/vascular endothelial growth factor (VEGF) signaling pathway by binding to phosphatase and tensin homolog (PTEN). Sprague Dawley (SD) rats were used for establishment of DR models. Target relationship between miR-21 and PTEN was assessed by bioinformatics prediction in combination with dual-luciferase reporter gene assay. Identification of expression of miR-21, PTEN and PI3K/Akt/VEGF signaling pathway-related genes in the retinal tissues was then conducted. In order to assess the contributory role of miR-21 in DR, the RVECs were transfected with mimic or inhibitor of miR-21, or siRNA-PTEN, followed by the detection of expression of PTEN and PI3K/Akt/VEGF-related genes, as well as the measurement of cell viability, cell cycle and apoptosis. Increased expression of miR-21 and PI3K/Akt/VEGF related genes, along with a reduced expression of PTEN was observed in the retinal tissues of DR rats. PTEN was targeted and negatively regulated by miR-21, while the PI3K/Akt/VEGF signaling pathway was activated by miR-21. RVECs transfected with miR-21 inhibitor exhibited promoted viability and angiogenesis, and inhibited apoptosis. To conclude, our results indicated that miR-21 overexpression could potentially stimulate RVEC viability and angiogenesis in rats with DR through activation of the PI3K/Akt/VEGF signaling pathway via repressing PTEN expression, highlighting the potential of miR-21 as a target for DR treatment. |
| Databáze: | OpenAIRE |
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