Integrated Analysis of M6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse

Overview

Journal Front Genet

Date 2020 Dec 17

PMID 33329722

Citations 14

Authors

Jianxiao Shen

Wanpeng Wang

Xinghua Shao

Jingkui Wu

Shu Li

Xiajing Che

Zhaohui Ni

Affiliations

Soon will be listed here.

Abstract

Background: N6-methyladenosine (m6A) is the most abundant modification known in mRNAs. It participates in a variety of physiological and pathological processes, such as metabolism, inflammation, and apoptosis.

Aims: To explore the mechanism of m6A in cisplatin-induced acute kidney injury (AKI) and berberine alleviation in mouse.

Methods: This study investigated the N6-methyladenosine (m6A) methylome of kidneys from three mouse groups: C57 mice (controls), those with CI-AKI (injury group, IG), and those pretreated with berberine (treatment group, TG). Methylated RNA Immunoprecipitation Next Generation Sequencing (MeRIP-seq) and RNA-seq were performed to identify the differences between the injury group and the control group (IvC) and between the treatment group and the injury group (TvI). Western blotting was performed to identify the protein levels of candidate genes.

Results: In IvC, differentially methylated genes (DMGs) were enriched in metabolic processes and cell death. In TvI, DMGs were enriched in tissue development. Several genes involved in important pathways related to CI-AKI showed opposite methylation and expression trends in the IvC and TvI comparisons.

Conclusion: m6A plays an important role in cisplatin induced AKI and berberine may alleviate this process.

Citing Articles

Nephroprotective effects of substances of medicine food homology and traditional Chinese medicine phytochemicals against acute kidney injury.

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Berberine Mitigates Sepsis-Associated Acute Kidney Injury in Aged Rats by Preserving Mitochondrial Integrity and Inhibiting TLR4/NF-κB and NLRP3 Inflammasome Activations.

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Nucleic acid and protein methylation modification in renal diseases.

Jin J, Liu X, Shao W, Meng X Acta Pharmacol Sin. 2023; 45(4):661-673.

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The role of N-methyladenosine modification in acute and chronic kidney diseases.

Qi S, Song J, Chen L, Weng H Mol Med. 2023; 29(1):166.

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The role of N6-methyladenosine (mA) in kidney diseases.

You L, Chen H, Chen L, Lin Y, Wang B, Fan Y Front Med (Lausanne). 2023; 10:1247690.

PMID: 37841018 PMC: 10569431. DOI: 10.3389/fmed.2023.1247690.

References

Luo Z, Zhang Z, Tai L, Zhang L, Sun Z, Zhou L . Comprehensive analysis of differences of N-methyladenosine RNA methylomes between high-fat-fed and normal mouse livers. Epigenomics. 2019; 11(11):1267-1282. DOI: 10.2217/epi-2019-0009. View

Ruan H, Zhan Y, Hou J, Xu B, Chen B, Tian Y . Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells. Oncogene. 2017; 36(50):6906-6918. PMC: 5735301. DOI: 10.1038/onc.2017.296. View

Spitale R, Flynn R, Zhang Q, Crisalli P, Lee B, Jung J . Structural imprints in vivo decode RNA regulatory mechanisms. Nature. 2015; 519(7544):486-90. PMC: 4376618. DOI: 10.1038/nature14263. View

Kechin A, Boyarskikh U, Kel A, Filipenko M . cutPrimers: A New Tool for Accurate Cutting of Primers from Reads of Targeted Next Generation Sequencing. J Comput Biol. 2017; 24(11):1138-1143. DOI: 10.1089/cmb.2017.0096. View

Zhou J, Wan J, Gao X, Zhang X, Jaffrey S, Qian S . Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015; 526(7574):591-4. PMC: 4851248. DOI: 10.1038/nature15377. View

Cummings B, Schnellmann R . Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther. 2002; 302(1):8-17. DOI: 10.1124/jpet.302.1.8. View

Wang K, Feng X, Chai L, Cao S, Qiu F . The metabolism of berberine and its contribution to the pharmacological effects. Drug Metab Rev. 2017; 49(2):139-157. DOI: 10.1080/03602532.2017.1306544. View

Vilar R, Fish R, Casini A, Neerman-Arbez M . Fibrin(ogen) in human disease: both friend and foe. Haematologica. 2020; 105(2):284-296. PMC: 7012490. DOI: 10.3324/haematol.2019.236901. View

Ahmad S, Hussain A, Hussain A, Abdullah I, Ali M, Froeyen M . Quantification of Berberine in L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity. Antioxidants (Basel). 2019; 8(6). PMC: 6616455. DOI: 10.3390/antiox8060185. View

10.

Li H, Tong J, Zhu S, Batista P, Duffy E, Zhao J . mA mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature. 2017; 548(7667):338-342. PMC: 5729908. DOI: 10.1038/nature23450. View

11.

Xu Y, Yuan X, Wu J, Chen R, Xia L, Zhang M . The N6-methyladenosine mRNA methylase METTL14 promotes renal ischemic reperfusion injury via suppressing YAP1. J Cell Biochem. 2019; 121(1):524-533. DOI: 10.1002/jcb.29258. View

12.

Shen L, Shao N, Liu X, Maze I, Feng J, Nestler E . diffReps: detecting differential chromatin modification sites from ChIP-seq data with biological replicates. PLoS One. 2013; 8(6):e65598. PMC: 3677880. DOI: 10.1371/journal.pone.0065598. View

13.

Leemans J, Stokman G, Claessen N, Rouschop K, Teske G, Kirschning C . Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J Clin Invest. 2005; 115(10):2894-903. PMC: 1201659. DOI: 10.1172/JCI22832. View

14.

Long Y, Zhen X, Zhu F, Hu Z, Lei W, Li S . Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury. Int J Biol Sci. 2017; 13(2):219-231. PMC: 5332876. DOI: 10.7150/ijbs.16725. View

15.

George B, Joy M, Aleksunes L . Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy. Exp Biol Med (Maywood). 2017; 243(3):272-282. PMC: 5813872. DOI: 10.1177/1535370217745302. View

16.

Schiessl I, Rosenauer A, Kattler V, Minuth W, Oppermann M, Castrop H . Dietary salt intake modulates differential splicing of the Na-K-2Cl cotransporter NKCC2. Am J Physiol Renal Physiol. 2013; 305(8):F1139-48. DOI: 10.1152/ajprenal.00259.2013. View

17.

Wang Y, Zeng L, Liang C, Zan R, Ji W, Zhang Z . Integrated analysis of transcriptome-wide mA methylome of osteosarcoma stem cells enriched by chemotherapy. Epigenomics. 2019; 11(15):1693-1715. DOI: 10.2217/epi-2019-0262. View

18.

Yang L, Brooks C, Xiao S, Sabbisetti V, Yeung M, Hsiao L . KIM-1-mediated phagocytosis reduces acute injury to the kidney. J Clin Invest. 2015; 125(4):1620-36. PMC: 4396492. DOI: 10.1172/JCI75417. View

19.

Holditch S, Brown C, Lombardi A, Nguyen K, Edelstein C . Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury. Int J Mol Sci. 2019; 20(12). PMC: 6627318. DOI: 10.3390/ijms20123011. View

20.

Anders M, Chelysheva I, Goebel I, Trenkner T, Zhou J, Mao Y . Dynamic mA methylation facilitates mRNA triaging to stress granules. Life Sci Alliance. 2018; 1(4):e201800113. PMC: 6238392. DOI: 10.26508/lsa.201800113. View