Long Non-coding RNA ASncmtRNA-2 is Upregulated in Diabetic Kidneys and High Glucose-treated Mesangial Cells

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2017 Mar 30

PMID 28352334

Citations 26

Authors

Yan Gao

Zhao-Yu Chen

Yan Wang

Yan Liu

Jian-Xia Ma

Yu-Kun Li

Affiliations

Soon will be listed here.

Abstract

Diabetic nephropathy (DN) is one of the most frequent complications associated with type I and II diabetes mellitus. Kidneys from patients with DN are characterized by mesangial matrix expansion and increased thickness of the glomerular basement membrane, which are induced by reactive oxygen species (ROS) production. Previous studies have been conducted to investigate this; however, the detailed mechanism of DN progression remains to be elucidated. The present study evaluated the expression of antisense mitochondrial non-coding RNA-2 (ASncmtRNA-2) in an experimental DN model and cultured human mesangial cells. When mice that exhibited genetic type II diabetes developed DN, ASncmtRNA-2 expression was significantly increased (P=0.017) and was positively correlated with pro-fibrotic factor transforming growth factor β1 (TGFβ1) expression and its downstream gene, fibronectin. Inhibition of ROS through administration of the nitric oxide synthase inhibitor, NG-nitro-L-Arginine methylester (L-NAME), significantly reduced (P=0.022) the upregulation of ASncmtRNA-2 in DN. In cultured human renal mesangial cells (HRMCs), ASncmtRNA-2 was upregulated by high glucose stimuli in a time-dependent manner. Glucose-induced upregulation of ASncmtRNA-2 was also reduced by co-incubation of HRMCs with L-NAME. Notably, specific short hairpin RNA against ASncmtRNA-2 significantly downregulated the expression of TGFβ1 in HRMCs. The present study suggests that ASncmtRNA-2 is upregulated by ROS and may promote glomerular fibrosis in DN via positively regulating the expression of pro-fibrotic factors. These findings may provide novel potential therapeutic and preventative treatments for DN.

Citing Articles

The mitochondrial long non-coding RNA lncMtloop regulates mitochondrial transcription and suppresses Alzheimer's disease.

Xiong W, Xu K, Sun J, Liu S, Zhao B, Shi J EMBO J. 2024; 43(23):6001-6031.

PMID: 39424953 PMC: 11612450. DOI: 10.1038/s44318-024-00270-7.

Identification of heterogeneous subtypes and a prognostic model for gliomas based on mitochondrial dysfunction and oxidative stress-related genes.

Li J, Wang S, Chi X, He Q, Tao C, Ding Y Front Immunol. 2023; 14:1183475.

PMID: 37334354 PMC: 10272431. DOI: 10.3389/fimmu.2023.1183475.

LncRNAs regulate ferroptosis to affect diabetes and its complications.

Chen Q, Ji H, Lin Y, Chen Z, Liu Y, Jin L Front Physiol. 2022; 13:993904.

PMID: 36225311 PMC: 9548856. DOI: 10.3389/fphys.2022.993904.

LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression.

Chiu-Tsun Tang P, Zhang Y, Li J, Chan M, Chen J, Tang Y Noncoding RNA. 2022; 8(3).

PMID: 35736633 PMC: 9227532. DOI: 10.3390/ncrna8030036.

LncRNA136131 suppresses apoptosis of renal tubular epithelial cells in acute kidney injury by targeting the miR-378a-3p/Rab10 axis.

Wu Z, Pan J, Yang J, Zhang D Aging (Albany NY). 2022; 14(8):3666-3686.

PMID: 35482482 PMC: 9085219. DOI: 10.18632/aging.204036.

References

Bianchessi V, Badi I, Bertolotti M, Nigro P, DAlessandra Y, Capogrossi M . The mitochondrial lncRNA ASncmtRNA-2 is induced in aging and replicative senescence in Endothelial Cells. J Mol Cell Cardiol. 2015; 81:62-70. DOI: 10.1016/j.yjmcc.2015.01.012. View

Merline R, Lazaroski S, Babelova A, Tsalastra-Greul W, Pfeilschifter J, Schluter K . Decorin deficiency in diabetic mice: aggravation of nephropathy due to overexpression of profibrotic factors, enhanced apoptosis and mononuclear cell infiltration. J Physiol Pharmacol. 2010; 60 Suppl 4:5-13. PMC: 6714047. View

Forbes J, Cooper M . Mechanisms of diabetic complications. Physiol Rev. 2013; 93(1):137-88. DOI: 10.1152/physrev.00045.2011. View

Ding G, Wang F, Shu J, Tian S, Jiang Y, Zhang D . Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes. 2012; 61(5):1133-42. PMC: 3331740. DOI: 10.2337/db11-1314. View

Kornfeld J, Bruning J . Regulation of metabolism by long, non-coding RNAs. Front Genet. 2014; 5:57. PMC: 3971185. DOI: 10.3389/fgene.2014.00057. View

Zhang H, Chen Z, Wang X, Huang Z, He Z, Chen Y . Long non-coding RNA: a new player in cancer. J Hematol Oncol. 2013; 6:37. PMC: 3693878. DOI: 10.1186/1756-8722-6-37. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Pan X, Wang X, Wang X, Sun Z, Zhang X, Liang X . Nitric oxide regulates blastocyst hatching in mice. Int J Clin Exp Med. 2015; 8(5):6994-7001. PMC: 4509181. View

Chandel N, Budinger G . The cellular basis for diverse responses to oxygen. Free Radic Biol Med. 2006; 42(2):165-74. DOI: 10.1016/j.freeradbiomed.2006.10.048. View

10.

Remuzzi G, Macia M, Ruggenenti P . Prevention and treatment of diabetic renal disease in type 2 diabetes: the BENEDICT study. J Am Soc Nephrol. 2006; 17(4 Suppl 2):S90-7. DOI: 10.1681/ASN.2005121324. View

11.

Burzio V, Villota C, Villegas J, Landerer E, Boccardo E, Villa L . Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells. Proc Natl Acad Sci U S A. 2009; 106(23):9430-4. PMC: 2695051. DOI: 10.1073/pnas.0903086106. View

12.

Brownlee M . The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005; 54(6):1615-25. DOI: 10.2337/diabetes.54.6.1615. View

13.

Collins A, Foley R, Chavers B, Gilbertson D, Herzog C, Johansen K . 'United States Renal Data System 2011 Annual Data Report: Atlas of chronic kidney disease & end-stage renal disease in the United States. Am J Kidney Dis. 2011; 59(1 Suppl 1):A7, e1-420. DOI: 10.1053/j.ajkd.2011.11.015. View

14.

Gibb E, Warren R, Wilson G, Brown S, Robertson G, Morin G . Activation of an endogenous retrovirus-associated long non-coding RNA in human adenocarcinoma. Genome Med. 2015; 7(1):22. PMC: 4375928. DOI: 10.1186/s13073-015-0142-6. View

15.

Motterle A, Gattesco S, Caille D, Meda P, Regazzi R . Involvement of long non-coding RNAs in beta cell failure at the onset of type 1 diabetes in NOD mice. Diabetologia. 2015; 58(8):1827-35. DOI: 10.1007/s00125-015-3641-5. View

16.

Tian Y, An L, Jiang L, Duan Y, Chen J, Jiang B . Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures. Life Sci. 2006; 80(3):193-9. DOI: 10.1016/j.lfs.2006.09.010. View

17.

Hung C, Wang L, Yu Y, Chen H, Srivastava S, Petrovics G . A long noncoding RNA connects c-Myc to tumor metabolism. Proc Natl Acad Sci U S A. 2014; 111(52):18697-702. PMC: 4284533. DOI: 10.1073/pnas.1415669112. View

18.

Giacco F, Brownlee M . Oxidative stress and diabetic complications. Circ Res. 2010; 107(9):1058-70. PMC: 2996922. DOI: 10.1161/CIRCRESAHA.110.223545. View

19.

Guariguata L, Whiting D, Hambleton I, Beagley J, Linnenkamp U, Shaw J . Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103(2):137-49. DOI: 10.1016/j.diabres.2013.11.002. View

20.

Di Marco E, Jha J, Sharma A, Wilkinson-Berka J, Jandeleit-Dahm K, de Haan J . Are reactive oxygen species still the basis for diabetic complications?. Clin Sci (Lond). 2015; 129(2):199-216. DOI: 10.1042/CS20150093. View