MicroRNA Regulation for Inflammasomes in High Glucose-Treated ARPE-19 Cells

Overview

Journal J Ophthalmol

Publisher Wiley

Specialty Ophthalmology

Date 2024 Sep 2

PMID 39220230

Authors

Ji Hong Kim

Hyoseon Yu

Ji Hye Kang

Eun Hee Hong

Min Ho Kang

Mincheol Seong

Heeyoon Cho

Yong Un Shin

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes-induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR).

Methods: To establish diabetes-induced cell models, ARPE-19 cells were treated with high glucose. The expression levels of five miRNAs (miR-185, miR-17, miR-20a, miR-15a, and miR-15b) were measured in high glucose-treated ARPE-19 cells using real-time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR-17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR-17 mimic into high glucose-treated ARPE-19 cells.

Results: In high glucose-treated ARPE-19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR-17 mimic into high glucose-treated ARPE-19 cells, the levels of inflammasome components were significantly decreased.

Conclusions: This study investigated the relationship between miRNAs and inflammasomes in diabetes-induced cells using high glucose-treated ARPE-19 cells. These findings suggested that miR-17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR.

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References

Hazim R, Volland S, Yen A, Burgess B, Williams D . Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide. Exp Eye Res. 2018; 179:18-24. PMC: 6360117. DOI: 10.1016/j.exer.2018.10.009. View

Coucha M, Mohamed I, Elshaer S, Mbata O, Bartasis M, El-Remessy A . High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation: Role of endoplasmic-reticulum-stress. World J Diabetes. 2017; 8(2):56-65. PMC: 5320749. DOI: 10.4239/wjd.v8.i2.56. View

Aghaei M, Khodadadian A, Elham K, Nazari M, Babakhanzadeh E . Major miRNA Involved in Insulin Secretion and Production in Beta-Cells. Int J Gen Med. 2020; 13:89-97. PMC: 7071856. DOI: 10.2147/IJGM.S249011. View

Lerner A, Upton J, Praveen P, Ghosh R, Nakagawa Y, Igbaria A . IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 2012; 16(2):250-64. PMC: 4014071. DOI: 10.1016/j.cmet.2012.07.007. View

Huang A, Ji L, Huang Y, Yu Q, Li Y . miR-185-5p alleviates CCI-induced neuropathic pain by repressing NLRP3 inflammasome through dual targeting MyD88 and CXCR4. Int Immunopharmacol. 2022; 104:108508. DOI: 10.1016/j.intimp.2021.108508. View

Tezcan G, Martynova E, Gilazieva Z, McIntyre A, Rizvanov A, Khaiboullina S . MicroRNA Post-transcriptional Regulation of the NLRP3 Inflammasome in Immunopathologies. Front Pharmacol. 2019; 10:451. PMC: 6504709. DOI: 10.3389/fphar.2019.00451. View

Cho H, Hwang M, Hong E, Yu H, Park H, Koh S . Micro-RNAs in the aqueous humour of patients with diabetic macular oedema. Clin Exp Ophthalmol. 2020; 48(5):624-635. DOI: 10.1111/ceo.13750. View

Liu S, Tang G, Duan F, Zeng C, Gong J, Chen Y . MiR-17-5p Inhibits TXNIP/NLRP3 Inflammasome Pathway and Suppresses Pancreatic β-Cell Pyroptosis in Diabetic Mice. Front Cardiovasc Med. 2021; 8:768029. PMC: 8645844. DOI: 10.3389/fcvm.2021.768029. View

Joltikov K, Sesi C, de Castro V, Davila J, Anand R, Khan S . Disorganization of Retinal Inner Layers (DRIL) and Neuroretinal Dysfunction in Early Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2018; 59(13):5481-5486. PMC: 6735648. DOI: 10.1167/iovs.18-24955. View

10.

Cheung N, Mitchell P, Wong T . Diabetic retinopathy. Lancet. 2010; 376(9735):124-36. DOI: 10.1016/S0140-6736(09)62124-3. View

11.

Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G . The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009; 10(3):241-7. PMC: 2820724. DOI: 10.1038/ni.1703. View

12.

Lu L, Thai T, Calado D, Chaudhry A, Kubo M, Tanaka K . Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 2009; 30(1):80-91. PMC: 2654249. DOI: 10.1016/j.immuni.2008.11.010. View

13.

Wang B, Cui Y, Zhang Q, Wang S, Xu S . Selenomethionine alleviates LPS-induced JNK/NLRP3 inflammasome-dependent necroptosis by modulating miR-15a and oxidative stress in chicken lungs. Metallomics. 2021; 13(8). DOI: 10.1093/mtomcs/mfab048. View

14.

Dunn K, Putkey F, Hjelmeland L . ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp Eye Res. 1996; 62(2):155-69. DOI: 10.1006/exer.1996.0020. View

15.

Mariathasan S, Newton K, Monack D, Vucic D, French D, Lee W . Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004; 430(6996):213-8. DOI: 10.1038/nature02664. View

16.

Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J . Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2009; 11(2):136-40. DOI: 10.1038/ni.1831. View

17.

Kwon H, Kim Y, Park H, Son J, Choi H, Lee Y . Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury. J Stroke. 2021; 23(3):420-436. PMC: 8521247. DOI: 10.5853/jos.2021.00626. View

18.

Holtkamp G, Kijlstra A, Peek R, de Vos A . Retinal pigment epithelium-immune system interactions: cytokine production and cytokine-induced changes. Prog Retin Eye Res. 2000; 20(1):29-48. DOI: 10.1016/s1350-9462(00)00017-3. View

19.

Gora I, Ciechanowska A, Ladyzynski P . NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes. Cells. 2021; 10(2). PMC: 7913585. DOI: 10.3390/cells10020314. View

20.

Xu J, Chen X, Nie W . miR-15b-5p REGULATES THE NLRP3 INFLAMMASOME SIGNAL THROUGH TARGETING SIRT3 TO REGULATE HYPOXIA/REOXYGENATION-INDUCED CARDIOMYOCYTE PYROPTOSIS PROCESS. Shock. 2022; 58(2):147-157. DOI: 10.1097/SHK.0000000000001961. View