MiR-122 Promotes Diabetic Retinopathy Through Targeting TIMP3

Overview

Journal Anim Cells Syst (Seoul)

Specialty Biology

Date 2020 Nov 19

PMID 33209201

Citations 4

Authors

Mingliang Wang

Huifen Zheng

Xianbo Zhou

Jiwei Zhang

Guanghui Shao

Affiliations

Soon will be listed here.

Abstract

Diabetic retinopathy (DR) is a primary complication of diabetes mellitus. DR can cause severe vision loss for patients. miR-122 is elevated in DR patients, while its role in DR is unclear. Hence, the purpose of this study was to analyze the effect of miR-122 on the function of high glucose-induced REC cells and the underlying molecular mechanisms. In this study, our results revealed that miR-122 was up-regulated in high glucose-induced human retinal pigment epithelial cells (ARPE-19). High glucose decreased the cell viability of ARPE-19 cells, which was then restored by miR-122 knockdown. In addition, miR-122 knockdown suppressed apoptosis of high glucose-induced ARPE-19 cells. High glucose also inhibited B-cell lymphoma-2 (Bcl-2) level and increased cleaved caspase-3 level in ARPE-19 cells, which were reversed by miR-122 knockdown. Tissue inhibitor of metalloproteinases-3 (TIMP3) was a direct target of miR-122. TIMP3 was decreased in high glucose-induced ARPE-19 cells, and the decrease was abrogated by miR-122 knockdown. In addition, the effects of miR-122 overexpression in cell viability and apoptosis of high glucose-induced ARPE-19 were abolished by overexpression of TIMP3. In conclusion, the effect and mechanism of miR-122 on high glucose-induced ARPE-19 cells were demonstrated for the first time. miR-122 promoted diabetic retinopathy through targeting TIMP3, making miR-122 a promising target for diabetic retinopathy therapy.

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References

Hu Y, Liu Q, Zhang M, Yan Y, Yu H, Ge L . MicroRNA-362-3p attenuates motor deficit following spinal cord injury via targeting paired box gene 2. J Integr Neurosci. 2019; 18(1):57-64. DOI: 10.31083/j.jin.2019.01.12. View

Wu D, Wen X, Han X, Wang S, Wang Y, Shen M . MiR-142-3p Enhances Cell Viability and Inhibits Apoptosis by Targeting CDKN1B and TIMP3 Following Sciatic Nerve Injury. Cell Physiol Biochem. 2018; 46(6):2347-2357. DOI: 10.1159/000489626. View

Shafabakhsh R, Aghadavod E, Mobini M, Heidari-Soureshjani R, Asemi Z . Association between microRNAs expression and signaling pathways of inflammatory markers in diabetic retinopathy. J Cell Physiol. 2018; 234(6):7781-7787. DOI: 10.1002/jcp.27685. View

Fu X, Ou B . miR-152/LIN28B axis modulates high-glucose-induced angiogenesis in human retinal endothelial cells via VEGF signaling. J Cell Biochem. 2019; 121(2):954-962. DOI: 10.1002/jcb.28978. View

Rao M, Zhu Y, Zhou Y, Cong X, Feng L . MicroRNA-122 inhibits proliferation and invasion in gastric cancer by targeting CREB1. Am J Cancer Res. 2017; 7(2):323-333. PMC: 5336505. View

Hewing N, Weskamp G, Vermaat J, Farage E, Glomski K, Swendeman S . Intravitreal injection of TIMP3 or the EGFR inhibitor erlotinib offers protection from oxygen-induced retinopathy in mice. Invest Ophthalmol Vis Sci. 2013; 54(1):864-70. PMC: 3562132. DOI: 10.1167/iovs.12-10954. View

Stewart M . Treatment of diabetic retinopathy: Recent advances and unresolved challenges. World J Diabetes. 2016; 7(16):333-41. PMC: 4999649. DOI: 10.4239/wjd.v7.i16.333. View

Jiang Q, Zhu X, Liu X, Liu J . [Effect of MiR-200b on retinal endothelial cell function in high-glucose condition and the mechanism]. Nan Fang Yi Ke Da Xue Xue Bao. 2016; 36(4):577-81. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

10.

Bourne R, Jonas J, Flaxman S, Keeffe J, Leasher J, Naidoo K . Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe: 1990-2010. Br J Ophthalmol. 2014; 98(5):629-38. DOI: 10.1136/bjophthalmol-2013-304033. View

11.

Wang J, Zhang J, Chen X, Yang Y, Wang F, Li W . miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress. Exp Eye Res. 2017; 168:89-99. DOI: 10.1016/j.exer.2017.11.006. View

12.

Thounaojam M, Jadeja R, Warren M, Powell F, Raju R, Gutsaeva D . MicroRNA-34a (miR-34a) Mediates Retinal Endothelial Cell Premature Senescence through Mitochondrial Dysfunction and Loss of Antioxidant Activities. Antioxidants (Basel). 2019; 8(9). PMC: 6769710. DOI: 10.3390/antiox8090328. View

13.

Guo D, Ma J, Li T, Yan L . Up-regulation of miR-122 protects against neuronal cell death in ischemic stroke through the heat shock protein 70-dependent NF-κB pathway by targeting FOXO3. Exp Cell Res. 2018; 369(1):34-42. DOI: 10.1016/j.yexcr.2018.04.027. View

14.

Zhao J, Gao S, Zhu Y, Shen X . Significant role of microRNA‑219‑5p in diabetic retinopathy and its mechanism of action. Mol Med Rep. 2018; 18(1):385-390. DOI: 10.3892/mmr.2018.8988. View

15.

Xiao H, Liu Z . Effects of microRNA‑217 on high glucose‑induced inflammation and apoptosis of human retinal pigment epithelial cells (ARPE‑19) and its underlying mechanism. Mol Med Rep. 2019; 20(6):5125-5133. PMC: 6854520. DOI: 10.3892/mmr.2019.10778. View

16.

Rosewell K, Li F, Puttabyatappa M, Akin J, Brannstrom M, Curry Jr T . Ovarian expression, localization, and function of tissue inhibitor of metalloproteinase 3 (TIMP3) during the periovulatory period of the human menstrual cycle. Biol Reprod. 2013; 89(5):121. PMC: 4434989. DOI: 10.1095/biolreprod.112.106989. View

17.

Qi J, Anand-Apte B . Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism. Apoptosis. 2015; 20(4):523-34. PMC: 4351133. DOI: 10.1007/s10495-014-1076-y. View

18.

Schmidt A . Highlighting Diabetes Mellitus: The Epidemic Continues. Arterioscler Thromb Vasc Biol. 2017; 38(1):e1-e8. PMC: 5776687. DOI: 10.1161/ATVBAHA.117.310221. View

19.

Wang B, Wang H, Yang Z . MiR-122 inhibits cell proliferation and tumorigenesis of breast cancer by targeting IGF1R. PLoS One. 2012; 7(10):e47053. PMC: 3466252. DOI: 10.1371/journal.pone.0047053. View

20.

Wang C, Yuan J, Qin D, Gu J, Zhao B, Zhang L . Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats. J Ethnopharmacol. 2016; 185:162-70. DOI: 10.1016/j.jep.2016.03.026. View