MiR-221/SIRT1/Nrf2 Signal Axis Regulates High Glucose Induced Apoptosis in Human Retinal Microvascular Endothelial Cells

Overview

Journal BMC Ophthalmol

Publisher Biomed Central

Specialty Ophthalmology

Date 2020 Jul 24

PMID 32698791

Citations 14

Authors

Bin Chen

Li Wu

Ting Cao

Hong-Mei Zheng

Tao He

Affiliations

Soon will be listed here.

Abstract

Background: Diabetic retinopathy (DR) is a serious symptom associated with diabetes and could cause much suffer to patients. MiR-221, SIRT1 and Nrf2 were associated with apoptosis and proliferation and their expression were altered in DR patients. However, their roles and regulatory mechanisms in human retinal microvascular endothelial cells (hRMEC) were not clear.

Methods: Expression of mRNA was detected by qRT-PCR. Protein expression was detected by Western blot. Interaction between miR-221 and SIRT1 was predicted by bioinformatics analysis and validated by dual-luciferase reporter assay. We analyzed the viability and apoptosis of hRMEC by MTT assay and FACS assay, respectively.

Results: High glucose (HG) treatment enhanced expression of miR-221 and inhibited expression of SIRT1 and Nrf2. MiR-221 overexpression promoted apoptosis under HG condition. Moreover, miR-221 directly interacted with mRNA of SIRT1 and inhibited SIRT1 expression in hRMEC, through which miR-221 inhibited Nrf2 pathway and induced apoptosis of hRMEC.

Conclusion: Our data demonstrated that miR-221/SIRT1/Nrf2 signal axis could promote apoptosis in hRMEC under HG conditions. This finding could provide theoretical support for future studies and may contribute to development of new treatment options to retard the process of DR development.

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References

Mazzeo A, Lopatina T, Gai C, Trento M, Porta M, Beltramo E . Functional analysis of miR-21-3p, miR-30b-5p and miR-150-5p shuttled by extracellular vesicles from diabetic subjects reveals their association with diabetic retinopathy. Exp Eye Res. 2019; 184:56-63. DOI: 10.1016/j.exer.2019.04.015. View

Mishra M, Duraisamy A, Kowluru R . Sirt1: A Guardian of the Development of Diabetic Retinopathy. Diabetes. 2018; 67(4):745-754. PMC: 5860853. DOI: 10.2337/db17-0996. View

He M, Long P, Yan W, Chen T, Guo L, Zhang Z . ALDH2 attenuates early-stage STZ-induced aged diabetic rats retinas damage via Sirt1/Nrf2 pathway. Life Sci. 2018; 215:227-235. DOI: 10.1016/j.lfs.2018.10.019. View

Wang T, Jiang L, Wei X, Dong Z, Liu B, Zhao J . Inhibition of miR-221 alleviates LPS-induced acute lung injury via inactivation of SOCS1/NF-κB signaling pathway. Cell Cycle. 2019; 18(16):1893-1907. PMC: 6681774. DOI: 10.1080/15384101.2019.1632136. View

Antosik K, Borowiec M . Genetic Factors of Diabetes. Arch Immunol Ther Exp (Warsz). 2017; 64(Suppl 1):157-160. DOI: 10.1007/s00005-016-0432-8. View

Xu P, Palmer L, Lechauve C, Zhao G, Yao Y, Luan J . Regulation of gene expression by miR-144/451 during mouse erythropoiesis. Blood. 2019; 133(23):2518-2528. PMC: 6557621. DOI: 10.1182/blood.2018854604. View

Murakami S, Motohashi H . Roles of Nrf2 in cell proliferation and differentiation. Free Radic Biol Med. 2015; 88(Pt B):168-178. DOI: 10.1016/j.freeradbiomed.2015.06.030. View

Monaghan K, McNaughten J, McGahon M, Kelly C, Kyle D, Yong P . Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium. PLoS One. 2015; 10(6):e0128359. PMC: 4457535. DOI: 10.1371/journal.pone.0128359. View

Meng Q, Chen R, Chen C, Su K, Li W, Tang L . Transcription factors Nrf2 and NF-κB contribute to inflammation and apoptosis induced by intestinal ischemia-reperfusion in mice. Int J Mol Med. 2017; 40(6):1731-1740. PMC: 5716448. DOI: 10.3892/ijmm.2017.3170. View

10.

Fornari F, Pollutri D, Patrizi C, La Bella T, Marinelli S, Casadei Gardini A . In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3-Mediated Apoptosis. Clin Cancer Res. 2017; 23(14):3953-3965. DOI: 10.1158/1078-0432.CCR-16-1464. View

11.

Marchev A, Dimitrova P, Burns A, Kostov R, Dinkova-Kostova A, Georgiev M . Oxidative stress and chronic inflammation in osteoarthritis: can NRF2 counteract these partners in crime?. Ann N Y Acad Sci. 2017; 1401(1):114-135. DOI: 10.1111/nyas.13407. View

12.

Garcia de la Torre N, Fernandez-Durango R, Gomez R, Fuentes M, Roldan-Pallares M, Donate J . Expression of Angiogenic MicroRNAs in Endothelial Progenitor Cells From Type 1 Diabetic Patients With and Without Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2015; 56(6):4090-8. DOI: 10.1167/iovs.15-16498. View

13.

Chen M, Wang W, Ma J, Ye P, Wang K . High glucose induces mitochondrial dysfunction and apoptosis in human retinal pigment epithelium cells via promoting SOCS1 and Fas/FasL signaling. Cytokine. 2015; 78:94-102. DOI: 10.1016/j.cyto.2015.09.014. View

14.

Wang C, Qu Z, Kong L, Xu L, Zhang M, Liu J . RETRACTED: Quercetin ameliorates lipopolysaccharide-caused inflammatory damage via down-regulation of miR-221 in WI-38 cells. Exp Mol Pathol. 2019; 108:1-8. DOI: 10.1016/j.yexmp.2019.03.002. View

15.

Zhang H, Sun Y, Rong W, Fan L, Cai Y, Qu Q . miR-221 participates in the airway epithelial cells injury in asthma via targeting SIRT1. Exp Lung Res. 2019; 44(6):272-279. DOI: 10.1080/01902148.2018.1533051. View

16.

Chen S, Yuan M, Liu Y, Zhao X, Lian P, Chen Y . Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next-generation sequencing. Clin Exp Ophthalmol. 2019; 47(7):925-936. DOI: 10.1111/ceo.13554. View

17.

Karaa A, Goldstein A . The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes. Pediatr Diabetes. 2014; 16(1):1-9. DOI: 10.1111/pedi.12223. View

18.

Gong Q, Li F, Xie J, Su G . Upregulated VEGF and Robo4 correlate with the reduction of miR-15a in the development of diabetic retinopathy. Endocrine. 2019; 65(1):35-45. PMC: 6606763. DOI: 10.1007/s12020-019-01921-0. View

19.

Li M, Yu H, Pan H, Zhou X, Ruan Q, Kong D . Nrf2 Suppression Delays Diabetic Wound Healing Through Sustained Oxidative Stress and Inflammation. Front Pharmacol. 2019; 10:1099. PMC: 6763603. DOI: 10.3389/fphar.2019.01099. View

20.

Huang W, Yan Z, Li D, Ma Y, Zhou J, Sui Z . Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells. Oxid Med Cell Longev. 2018; 2018:1862462. PMC: 5842687. DOI: 10.1155/2018/1862462. View