Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Extracellular Vesicle-Derived miR-26b-5p is Up-Regulated in the Serum of Patients with Diabetic Retinopathy

Author(s): Yuru Zhang, Jun Wei, Le Zhang, Guangwei Jiang, Bing Wang and Liping Jiang*

Volume 25, Issue 5, 2022

Published on: 16 February, 2021

Page: [877 - 882] Pages: 6

DOI: 10.2174/1386207324666210216092917

Price: $65

Abstract

Background: Diabetic retinopathy (DR) is a severe complication of diabetes; however, the pathogenesis of DR has not been completely clarified, which is mostly dependent on the molecular pathology. This study aimed to investigate key serum-derived miRNAs associated with DR.

Methods: miRNA expression profile arrays of human umbilical vein endothelial cells (HUVECs) treated with glucose were downloaded from the Gene Expression Omnibus (GEO) database (GSE74296). Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub miRNAs, which were verified in HUVECs treated with 40 mM and 5 mM glucose, respectively. Meanwhile, serum samples of patients with DR and healthy controls were collected, and EVs were extracted from the patients’ serum by ultracentrifugation. Hub miRNAs associated with endothelial dysfunction were verified in healthy individuals before and after treatment of patients with DR, by qRT-PCR.

Results: These miRNAs were categorized into six modules, among which miR-26b-5p had a strong association with other modules. This miRNA was also one of the hyperglycemia-induced miRNAs related to endothelial dysfunction. miR-26b-5p was up-regulated in HUVECs treated with 40 mM glucose and in the serum of patients with DR before and after treatment. Furthermore, miR- 26b-5p was slightly up-regulated in serum-derived EVs but not in serum without EVs in DM patients.

Conclusion: Our results suggest that EVs derived from miR-26b-5p are up-regulated in the serum of patients with DR.

Keywords: miR-26b-5p, diabetic retinopathy, extracellular vesicles, hyperglycemia, WGCNA, serum.

Graphical Abstract

[1]
Mi, W.; Xia, Y.; Bian, Y. Meta-analysis of the association between aldose reductase gene (CA)n microsatellite variants and risk of diabetic retinopathy. Exp. Ther. Med., 2019, 18(6), 4499-4509.
[http://dx.doi.org/10.3892/etm.2019.8086] [PMID: 31777552]
[2]
Ellis, M.P.; Lent-Schochet, D.; Lo, T.; Yiu, G. Emerging concepts in the treatment of diabetic retinopathy. Curr. Diab. Rep., 2019, 19(11), 137.
[http://dx.doi.org/10.1007/s11892-019-1276-5] [PMID: 31748965]
[3]
Backes, C.; Meese, E.; Keller, A. Specific miRNA disease biomarkers in blood, serum and plasma: challenges and prospects. Mol. Diagn. Ther., 2016, 20(6), 509-518.
[http://dx.doi.org/10.1007/s40291-016-0221-4] [PMID: 27378479]
[4]
Cui, C.; Li, Y.; Liu, Y. Down-regulation of miR-377 suppresses high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells by direct up-regulation of target gene SIRT1. Hum. Cell, 2019, 32(3), 260-274.
[http://dx.doi.org/10.1007/s13577-019-00240-w] [PMID: 30706373]
[5]
Dai, C.; Jiang, S.; Chu, C.; Xin, M.; Song, X.; Zhao, B. Baicalin protects human retinal pigment epithelial cell lines against high glucose-induced cell injury by up-regulation of microRNA-145. Exp. Mol. Pathol., 2019, 106, 123-130.
[http://dx.doi.org/10.1016/j.yexmp.2019.01.002] [PMID: 30625293]
[6]
Shao, Y.; Dong, L.J.; Takahashi, Y.; Chen, J.; Liu, X.; Chen, Q.; Ma, J.X.; Li, X.R. miRNA-451a regulates RPE function through promoting mitochondrial function in proliferative diabetic retinopathy. Am. J. Physiol. Endocrinol. Metab., 2019, 316(3), E443-E452.
[http://dx.doi.org/10.1152/ajpendo.00360.2018] [PMID: 30576241]
[7]
Murinello, S.; Usui, Y.; Sakimoto, S.; Kitano, M.; Aguilar, E.; Friedlander, H.M.; Schricker, A.; Wittgrove, C.; Wakabayashi, Y.; Dorrell, M.I.; Westenskow, P.D.; Friedlander, M. miR-30a-5p inhibition promotes interaction of Fas+ endothelial cells and FasL+ microglia to decrease pathological neovascularization and promote physiological angiogenesis. Glia, 2019, 67(2), 332-344.
[http://dx.doi.org/10.1002/glia.23543] [PMID: 30484883]
[8]
Jochmann, C.; Hammes, H.P. Epidemiology, pathogenesis and therapy of diabetic retinopathy and maculopathy. Z. Arztl. Fortbild. Qualitatssich., 2002, 96(3), 167-174.
[PMID: 12017760]
[9]
Silambarasan, M.; Tan, J.R.; Karolina, D.S.; Armugam, A.; Kaur, C.; Jeyaseelan, K. MicroRNAs in hyperglycemia induced endothelial cell dysfunction. Int. J. Mol. Sci., 2016, 17(4), 518.
[http://dx.doi.org/10.3390/ijms17040518] [PMID: 27070575]
[10]
Zhou, X.G.; Huang, X.L.; Liang, S.Y.; Tang, S.M.; Wu, S.K.; Huang, T.T.; Mo, Z.N.; Wang, Q.Y. Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis. OncoTargets Ther., 2018, 11, 2815-2830.
[http://dx.doi.org/10.2147/OTT.S163891] [PMID: 29844680]
[11]
Walker, A.L.; Steward, S.; Howard, T.A.; Mortier, N.; Smeltzer, M.; Wang, Y.D.; Ware, R.E. Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia. Blood, 2011, 118(20), 5664-5670.
[http://dx.doi.org/10.1182/blood-2011-07-368746] [PMID: 21921042]
[12]
Godo, S.; Shimokawa, H. Endothelial functions. Arterioscler. Thromb. Vasc. Biol., 2017, 37(9), e108-e114.
[http://dx.doi.org/10.1161/ATVBAHA.117.309813] [PMID: 28835487]
[13]
Guan, G.; Han, H.; Yang, Y.; Jin, Y.; Wang, X.; Liu, X. Neferine prevented hyperglycemia-induced endothelial cell apoptosis through suppressing ROS/Akt/NF-κB signal. Endocrine, 2014, 47(3), 764-771.
[http://dx.doi.org/10.1007/s12020-014-0186-1] [PMID: 24590293]
[14]
Stępień, E.Ł.; Durak-Kozica, M.; Kamińska, A.; Targosz-Korecka, M.; Libera, M.; Tylko, G.; Opalińska, A.; Kapusta, M.; Solnica, B.; Georgescu, A.; Costa, M.C.; Czyżewska-Buczyńska, A.; Witkiewicz, W.; Małecki, M.T.; Enguita, F.J. Circulating ectosomes: Determination of angiogenic microRNAs in type 2 diabetes. Theranostics, 2018, 8(14), 3874-3890.
[http://dx.doi.org/10.7150/thno.23334] [PMID: 30083267]
[15]
Cheung, L.; Fisher, R.M.; Kuzmina, N.; Li, D.; Li, X.; Werngren, O.; Blomqvist, L.; Ståhle, M.; Landén, N.X. Psoriasis skin inflammation-induced microRNA-26b targets NCEH1 in underlying subcutaneous adipose tissue. J. Invest. Dermatol., 2016, 136(3), 640-648.
[http://dx.doi.org/10.1016/j.jid.2015.12.008] [PMID: 27015452]
[16]
Demirsoy, İ.H.; Ertural, D.Y.; Balci, Ş.; Çınkır, Ü.; Sezer, K.; Tamer, L.; Aras, N. Profiles of Circulating MiRNAs Following metformin treatment in patients with type 2 diabetes. J. Med. Biochem., 2018, 37(4), 499-506.
[http://dx.doi.org/10.2478/jomb-2018-0009] [PMID: 30584410]
[17]
Tang, C.M.; Zhang, M.; Huang, L.; Hu, Z.Q.; Zhu, J.N.; Xiao, Z.; Zhang, Z.; Lin, Q.X.; Zheng, X.L.; Yang, M.; Wu, S.L.; Cheng, J.D.; Shan, Z.X. CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts. Sci. Rep., 2017, 12(7), 40342.
[18]
Zhou, A.; Pan, H.; Sun, D.; Xu, H.; Zhang, C.; Chen, X.; Li, L.; Wang, T. miR-26b-5p Inhibits the proliferation, migration and invasion of human papillary thyroid cancer in a β-Catenin-dependent manner. OncoTargets Ther., 2020, 13, 1593-1603.
[http://dx.doi.org/10.2147/OTT.S236319] [PMID: 32110056]
[19]
Jia, C.M.; Tian, Y.Y.; Quan, L.N.; Jiang, L.; Liu, A.C. miR-26b-5p suppresses proliferation and promotes apoptosis in multiple myeloma cells by targeting JAG1. Pathol. Res. Pract., 2018, 214(9), 1388-1394.
[http://dx.doi.org/10.1016/j.prp.2018.07.025] [PMID: 30098829]
[20]
Du, J.; Han, R.; Li, Y.; Liu, X.; Liu, S.; Cai, Z.; Xu, Z.; Li, Y.; Yuan, X.; Guo, X.; Lu, B.; Sun, K. LncRNA HCG11/miR-26b-5p/QKI5 feedback loop reversed high glucose-induced proliferation and angiogenesis inhibition of HUVECs. J. Cell. Mol. Med., 2020, 24(24), 14231-1446.
[http://dx.doi.org/10.1111/jcmm.16040] [PMID: 33128346]
[21]
Yang, L.; Dong, C.; Yang, J.; Yang, L.; Chang, N.; Qi, C.; Li, L. MicroRNA-26b-5p inhibits mouse liver fibrogenesis and angiogenesis by targeting PDGF receptor-beta. Mol. Ther. Nucleic Acids, 2019, 16, 206-217.
[http://dx.doi.org/10.1016/j.omtn.2019.02.014] [PMID: 30901579]
[22]
Mastropasqua, R.; D’Aloisio, R.; Di Antonio, L.; Erroi, E.; Borrelli, E.; Evangelista, F.; D’Onofrio, G.; Di Nicola, M.; Di Martino, G.; Toto, L. Widefield optical coherence tomography angiography in diabetic retinopathy. Acta Diabetol., 2019, 56(12), 1293-1303.
[http://dx.doi.org/10.1007/s00592-019-01410-w] [PMID: 31468199]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy