miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
Zhenyu Ji,1 Jinyuan Luo,1 Ting Su,2 Changzheng Chen,1 Yu Su1 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 2Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of C...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/70cb300e066b405495bdcb591956f81c |
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| Sumario: | Zhenyu Ji,1 Jinyuan Luo,1 Ting Su,2 Changzheng Chen,1 Yu Su1 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 2Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of ChinaCorrespondence: Yu SuDepartment of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of ChinaTel/Fax +86-2788041911Email sy_daisy1206@163.comIntroduction: Diabetic retinopathy (DR) is one of the major leading causes for vision loss globally. Current study illustrates the role of miR-7a in DR.Material and Methods: Retinal pericytes (RPs) and Endothelial cells (ECs) were isolated from mouse model of DR. qRT-PCR was done for expression of miR-7a and target gene mRNA, Western blot for protein expression. Identification of miR-7a target gene was done by TargetScan and Luciferase assay. Cell viability and invasion was done by MTT and Transwell chamber assay.Results: The expression of miR-7a was down-regulated whereas level of IRS-2 was unregulated in isolated RPs and ECs. Luciferase assay suggested correlation between miR-7a and IRS-2, over-expression of miR-7a using a mimic resulted in suppression in viability and invasion capacity of RPs and ECs and inhibited the protein levels of PI3K/Akt cascade and IRS-2, and however the inhibitor reversed them respectively. Transfection of siRNA targeting IRS-2 caused alteration in miR-7a mediated changes in ECs suggesting that miR-7a may decrease angiogenesis in DR by inhibiting the levels of IRS-2.Conclusion: miR-7a suppresses PI3K/Akt cascade via targeting IRS-2, thus decreasing the viability and invasion capacity of RPs and ECs, suggesting an interesting treatment target for DR.Keywords: miR-7a, diabetic retinopathy; DR, IRS-2, PI3K/Akt, endothelial cells; ECs, retinal pericytes; RPs |
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