MicroRNA-98-5p inhibits human mesangial cell proliferation and TNF-α and IL‑6 secretion by targeting BTB and CNC homology 1

Du,Yong; Shi,Xiaoqiang; Li,Jing; Jia,Yanhui

doi:10.3892/etm.2021.10871

MicroRNA-98-5p inhibits human mesangial cell proliferation and TNF-α and IL‑6 secretion by targeting BTB and CNC homology 1

Authors:
- Yong Du
- Xiaoqiang Shi
- Jing Li
- Yanhui Jia
View Affiliations

Affiliations: Department of Rheumatology and Immunology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China, Department of Urology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China, Department of Nephrology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
Published online on: October 12, 2021 https://doi.org/10.3892/etm.2021.10871
Article Number: 1436
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNA (miR)‑98‑5p has been reported to be involved in the development of lupus nephritis (LN); however, its specific role in LN remains unclear. The present study aimed to investigate the effect of miR‑98‑5p on human mesangial cell proliferation and the secretion of TNF‑α and IL‑6. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting were used to analyze the level of gene and protein expression, respectively. Cellular proliferation was assessed using a Cell Counting Kit‑8 (CCK‑8) assay. ELISA was used to detect the secretion of TNF‑α and IL‑6 by human mesangial cells. RT‑qPCR analysis revealed that miR‑98‑5p expression was downregulated in LN renal tissues compared with control renal tissues. Overexpression of miR‑98‑5p inhibited human mesangial cell proliferation and the secretion of TNF‑α and IL‑6, whereas miR‑98‑5p‑knockdown demonstrated the opposite effect. Dual luciferase reporter assays demonstrated that miR‑98‑5p directly targeted BTB and CNC homology 1 (BACH1). BACH1‑overexpression promoted human mesangial cell proliferation and the secretion of TNF‑α and IL‑6, whereas BACH1‑knockdown demonstrated the opposite effect. Notably, co‑transfection with miR‑98‑5p mimic inhibited BACH1‑overexpression induced human mesangial cell proliferation and the secretion of TNF‑α and IL‑6. The results of the present study indicated that miR‑98‑5p inhibited human mesangial cell proliferation and the secretion of TNF‑α and IL‑6 by targeting BACH1. Therefore, miR‑98‑5p and BACH1 may represent potential therapeutic targets for LN.

View Figures

View References

1	Talotta R, Atzeni F and Laska MJ: Therapeutic peptides for the treatment of systemic lupus erythematosus: A place in therapy. Expert Opin Investig Drugs. 29:845–867. 2020.PubMed/NCBI View Article : Google Scholar
2	Ramanujam M, Steffgen J, Visvanathan S, Mohan C, Fine JS and Putterman C: Phoenix from the flames: Rediscovering the role of the CD40-CD40L pathway in systemic lupus erythematosus and lupus nephritis. Autoimmun Rev. 19(102668)2020.PubMed/NCBI View Article : Google Scholar
3	Wang SF, Chen YH, Chen DQ, Liu ZZ, Xu F, Zeng CH and Hu WX: Mesangial proliferative lupus nephritis with podocytopathy: A special entity of lupus nephritis. Lupus. 27:303–311. 2018.PubMed/NCBI View Article : Google Scholar
4	Wofsy D, Hillson JL and Diamond B: Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials. Arthritis Rheum. 65:1586–1591. 2013.PubMed/NCBI View Article : Google Scholar
5	Wright RD, Dimou P, Northey SJ and Beresford MW: Mesangial cells are key contributors to the fibrotic damage seen in the lupus nephritis glomerulus. J Inflamm (Lond). 16(22)2019.PubMed/NCBI View Article : Google Scholar
6	Sung SJ and Fu SM: Interactions among glomerulus infiltrating macrophages and intrinsic cells via cytokines in chronic lupus glomerulonephritis. J Autoimmun. 106(102331)2020.PubMed/NCBI View Article : Google Scholar
7	Kong J, Li L, Lu Z, Song J, Yan J, Yang J, Gu Z and Da Z: Microrna-155 suppresses mesangial cell proliferation and tgf-β1 production via inhibiting cxcr5-erk signaling pathway in lupus nephritis. Inflammation. 42:255–263. 2019.PubMed/NCBI View Article : Google Scholar
8	Chen CC, Chang ZY, Tsai FJ and Chen SY: Resveratrol pretreatment ameliorates concanavalin a-induced advanced renal glomerulosclerosis in aged mice through upregulation of sirtuin 1-mediated klotho expression. Int J Mol Sci. 21(21)2020.PubMed/NCBI View Article : Google Scholar
9	Honarpisheh M, Köhler P, von Rauchhaupt E and Lech M: The involvement of micrornas in modulation of innate and adaptive immunity in systemic lupus erythematosus and lupus nephritis. J Immunol Res. 2018(4126106)2018.PubMed/NCBI View Article : Google Scholar
10	Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010.PubMed/NCBI View Article : Google Scholar
11	Wang Y, Bao W, Liu Y, Wang S, Xu S, Li X, Li Y and Wu S: miR-98-5p contributes to cisplatin resistance in epithelial ovarian cancer by suppressing miR-152 biogenesis via targeting Dicer1. Cell Death Dis. 9(447)2018.PubMed/NCBI View Article : Google Scholar
12	Yuan S, Tang C, Chen D, Li F, Huang M, Ye J, He Z, Li W, Chen Y, Lin X, et al: Mir-98 modulates cytokine production from human PBMCS in systemic lupus erythematosus by targeting IL-6 mRNA. J Immunol Res. 2019(9827574)2019.PubMed/NCBI View Article : Google Scholar
13	Xie L and Xu J: Role of mir-98 and its underlying mechanisms in systemic lupus erythematosus. J Rheumatol. 45:1397–1405. 2018.PubMed/NCBI View Article : Google Scholar
14	Wang Y, Yu F, Song D, Wang SX and Zhao MH: Podocyte involvement in lupus nephritis based on the 2003 ISN/RPS system: A large cohort study from a single centre. Rheumatology (Oxford). 53:1235–1244. 2014.PubMed/NCBI View Article : Google Scholar
15	Xu J, Xu G, Zhang T, Chen T, Zhao W and Wang G: NFIL3 Acts as a Nuclear Factor to Increase Osteosarcoma Progression. BioMed Res Int. 2019(4068521)2019.PubMed/NCBI View Article : Google Scholar
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
17	Mohr AM and Mott JL: Overview of microRNA biology. Semin Liver Dis. 35:3–11. 2015.PubMed/NCBI View Article : Google Scholar
18	Zhang L, Zhang X and Si F: MicroRNA-124 represents a novel diagnostic marker in human lupus nephritis and plays an inhibitory effect on the growth and inflammation of renal mesangial cells by targeting TRAF6. Int J Clin Exp Pathol. 12:1578–1588. 2019.PubMed/NCBI
19	Pan Y, Pan YM, Liu FT, Xu SL, Gu JT, Hang PZ and Du ZM: MicroRNA-98 ameliorates doxorubicin-induced cardiotoxicity via regulating caspase-8 dependent Fas/RIP3 pathway. Environ Toxicol Pharmacol. 85(103624)2021.PubMed/NCBI View Article : Google Scholar
20	Wang Q, Wei S, Zhou H, Li L, Zhou S, Shi C, Shi Y, Qiu J and Lu L: MicroRNA-98 Inhibits Hepatic Stellate Cell Activation and Attenuates Liver Fibrosis by Regulating HLF Expression. Front Cell Dev Biol. 8(513)2020.PubMed/NCBI View Article : Google Scholar
21	Zeng Y, Feng Z, Liao Y, Yang M, Bai Y and He Z: Diminution of microRNA-98 alleviates renal fibrosis in diabetic nephropathy by elevating Nedd4L and inactivating TGF-β/Smad2/3 pathway. Cell Cycle. 19:3406–3418. 2020.PubMed/NCBI View Article : Google Scholar
22	Sun X, Li X, Ma S, Guo Y and Li Y: MicroRNA-98-5p ameliorates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by inhibiting Bach1 and promoting Nrf2/ARE signaling. Biochem Biophys Res Commun. 507:114–121. 2018.PubMed/NCBI View Article : Google Scholar
23	Patil SL, Palat A, Pan Y, Rajapakshe K, Mirchandani R, Bondesson M, Yustein JT, Coarfa C and Gunaratne PH: MicroRNA-509-3p inhibits cellular migration, invasion, and proliferation, and sensitizes osteosarcoma to cisplatin. Sci Rep. 9(19089)2019.PubMed/NCBI View Article : Google Scholar
24	Kanezaki R, Toki T, Yokoyama M, Yomogida K, Sugiyama K, Yamamoto M, Igarashi K and Ito E: Transcription factor BACH1 is recruited to the nucleus by its novel alternative spliced isoform. J Biol Chem. 276:7278–7284. 2001.PubMed/NCBI View Article : Google Scholar
25	Warnatz HJ, Schmidt D, Manke T, Piccini I, Sultan M, Borodina T, Balzereit D, Wruck W, Soldatov A, Vingron M, et al: The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle. J Biol Chem. 286:23521–23532. 2011.PubMed/NCBI View Article : Google Scholar
26	Kishimoto D, Kirino Y, Tamura M, Takeno M, Kunishita Y, Takase-Minegishi K, Nakano H, Kato I, Nagahama K, Yoshimi R, et al: Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons. Arthritis Res Ther. 20(64)2018.PubMed/NCBI View Article : Google Scholar
27	Yap DYH, Yung S, Lee P, Yam IYL, Tam C, Tang C and Chan TM: B Cell Subsets and Cellular Signatures and Disease Relapse in Lupus Nephritis. Front Immunol. 11(1732)2020.PubMed/NCBI View Article : Google Scholar
28	Liu Y, Yu C, Ji K, Wang X, Li X, Xie H, Wang Y, Huang Y, Qi D and Fan H: Quercetin reduces TNF-α-induced mesangial cell proliferation and inhibits PTX3 production: Involvement of NF-κB signaling pathway. Phytother Res. 33:2401–2408. 2019.PubMed/NCBI View Article : Google Scholar
29	Sun J, Guo S, Niu F, Liu D and Zhuang Y: Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway. Mol Med Rep. 22:5436–5443. 2020.PubMed/NCBI View Article : Google Scholar