Mechanism of circHIPK3-miRNA-124-3p/miRNA-148b-3p-Mediated Inflammatory Responses and Cell Senescence in Candida albicans-Induced Septic Acute Kidney Injury

Experimental Section: Research Article

Han J.a,b· Li W.a,b· Zhang J.a,b· Guan Y.a,b· Huang Y.a,b· Li X.a,b

Author affiliations

aDepartment of Critical Care Medicine, The Fifth Affiliated Hospital (Zhuhai) of Zunyi Medical University, Zhuhai, China
bDepartment of Emergency, The Fifth Affiliated Hospital (Zhuhai) of Zunyi Medical University, Zhuhai, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud Rent for 48h to view Buy Cloud Access for unlimited viewing via different devices Synchronizing in the ReadCube Cloud Printing and saving restrictions apply Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Experimental Section: Research Article

Received: November 12, 2021
Accepted: February 27, 2022
Published online: May 16, 2022

Number of Print Pages: 21
Number of Figures: 11
Number of Tables: 1

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: https://www.karger.com/GER

Abstract

Introduction: Sepsis is a life-threatening inflammatory state that can result in septic acute kidney injury (SAKI). Circular RNAs (circRNAs) are implicated in various inflammatory diseases including SAKI. This study investigated the effect of circHIPK3 on inflammatory responses and cell senescence in Candida albicans-induced SAKI. Methods: circHIPK3 expression and inflammatory factors in the serum of SAKI patients and healthy volunteers were detected. The murine and cell models of SAKI were established by C. albicans and lipopolysaccharide induction, respectively. The effect of circHIPK3 on SAKI inflammatory responses and cell senescence was measured using ELISA, SA-β-gal staining, CCK-8, RT-qPCR, and Western blot. The binding relationships among circHIPK3, miR-124-3p, or miR-148b-3p and KLF6 or DNMT1/3a were confirmed. The binding of KLF6 and NLRP3 was determined, and the methylation level of the Klotho promoter was detected. Functional rescue experiments were performed to verify the effect of miR-124-3p or miR-148b-3p on SAKI. Results: circHIPK3 was highly expressed in SAKI. circHIPK3 silencing alleviated kidney injury in SAKI mice and enhanced SAKI cell viability by alleviating inflammatory responses and cell senescence. Mechanically, circHIPK3 upregulated KLF6 expression by competitively binding to miR-124-3p, thereby promoting the binding of KLF6 and NLRP3, activating NLRP3/caspase-1-mediated pyroptosis, and eventually aggravating SAKI inflammatory responses. circHIPK3 upregulated DNMT1/3a expression by competitively binding to miR-148b-3p, thus elevating the methylation level of Klotho promoter and accelerating SAKI cell senescence. Downregulation of miR-124-3p or miR-148b-3p attenuated the protective effect of circHIPK3 silencing on SAKI. Conclusion: circHIPK3 aggravated SAKI inflammatory responses via miR-124-3p/KLF6 and accelerated SAKI cell senescence via miR-148b-3p/DNMT1/3a.

© 2022 S. Karger AG, Basel

References Peerapornratana S, Manrique-Caballero CL, Gómez H, Kellum JA. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int. 2019 Nov;96(5):1083–99. Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ. 2019 Jan 9;364:k4891. Shum HP, Yan WW, Chan TM. Recent knowledge on the pathophysiology of septic acute kidney injury: a narrative review. J Crit Care. 2016 Feb;31(1):82–9. Keir I, Kellum JA. Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations. J Vet Emerg Crit Care. 2015 Mar–Apr;25(2):200–9. Chen C, Qiu R, Yang J, Zhang Q, Sun G, Gao X, et al. Lipoxin A4 restores septic renal function via blocking crosstalk between inflammation and premature senescence. Front Immunol. 2021;12:637753. Andrade L, Rodrigues CE, Gomes SA, Noronha IL. Acute kidney injury as a condition of renal senescence. Cell Transplant. 2018 May;27(5):739–53. Ren GL, Zhu J, Li J, Meng XM. Noncoding RNAs in acute kidney injury. J Cell Physiol. 2019 Mar;234(3):2266–76. Liu Z, Wang Y, Shu S, Cai J, Tang C, Dong Z. Non-coding RNAs in kidney injury and repair. Am J Physiol Cell Physiol. 2019 Aug 1;317(2):C177–88. Jin J, Sun H, Shi C, Yang H, Wu Y, Li W, et al. Circular RNA in renal diseases. J Cell Mol Med. 2020 Jun;24(12):6523–33. Wang J, Li X, Liu Y, Peng C, Zhu H, Tu G, et al. CircHIPK3 promotes pyroptosis in acinar cells through regulation of the miR-193a-5p/GSDMD axis. Front Med. 2020;7:88. Lian C, Sun J, Guan W, Zhang L, Zhang X, Yang L, et al. Circular RNA circHIPK3 activates macrophage NLRP3 inflammasome and TLR4 pathway in gouty arthritis via sponging miR-561 and miR-192. Inflammation. 2021 Jun 4;44(5):2065–77. Liu R, Zhang M, Ge Y. Circular RNA HIPK3 exacerbates diabetic nephropathy and promotes proliferation by sponging miR-185. Gene. 2021 Jan 10;765:145065. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013 Mar 21;495(7441):333–8. Carbonell T, Gomes AV. MicroRNAs in the regulation of cellular redox status and its implications in myocardial ischemia-reperfusion injury. Redox Biol. 2020 Sep;36:101607. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013 Mar 21;495(7441):384–8. Li XY, Zhang YQ, Xu G, Li SH, Li H. miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis. Int J Mol Med. 2018 Jun;41(6):3468–76. Yu L, Gu T, Shi E, Wang Y, Fang Q, Wang C. Dysregulation of renal microRNA expression after deep hypothermic circulatory arrest in rats. Eur J Cardiothorac Surg. 2016 Jun;49(6):1725–31. National Research Council. Guide for the care and use of laboratory animals. 8th ed. Washington, DC: The National Academies Press; 2011. Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649–72. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250–6. Zheng C, Wu D, Shi S, Wang L. miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury. Ren Fail. 2021 Dec;43(1):291–301. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860–921. Li LC, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002 Nov;18(11):1427–31. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001 Dec;25(4):402–8. Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014 Jan;42(Database issue):D92–7. Muppirala UK, Honavar VG, Dobbs D. Predicting RNA-protein interactions using only sequence information. BMC Bioinformatics. 2011 Dec 22;12:489. Hong L, Ma X, Liu J, Luo Y, Lin J, Shen Y, et al. Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis. Pulm Circ. 2021 Apr–Jun;11(2):20458940211000234. Navarathna DH, Stein EV, Lessey-Morillon EC, Nayak D, Martin-Manso G, Roberts DD. CD47 promotes protective innate and adaptive immunity in a mouse model of disseminated candidiasis. PLoS One. 2015;10(5):e0128220. Ngo LY, Kasahara S, Kumasaka DK, Knoblaugh SE, Jhingran A, Hohl TM. Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis. J Infect Dis. 2014 Jan 1;209(1):109–19. Ferenbach DA, Bonventre JV. Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat Rev Nephrol. 2015 May;11(5):264–76. Lee BY, Han JA, Im JS, Morrone A, Johung K, Goodwin EC, et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell. 2006 Apr;5(2):187–95. Gary RK, Kindell SM. Quantitative assay of senescence-associated beta-galactosidase activity in mammalian cell extracts. Anal Biochem. 2005 Aug 15;343(2):329–34. Chkhotua AB, Abendroth D, Froeba G, Schelzig H. Up-regulation of cell cycle regulatory genes after renal ischemia/reperfusion: differential expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes depending on reperfusion time. Transpl Int. 2006 Jan;19(1):72–7. Davalos AR, Kawahara M, Malhotra GK, Schaum N, Huang J, Ved U, et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol. 2013 May 13;201(4):613–29. Cheng Z, Yu C, Cui S, Wang H, Jin H, Wang C, et al. circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1. Nat Commun. 2019 Jul 19;10(1):3200. Chen F, Hu Y, Xie Y, Zhao Z, Ma L, Li Z, et al. Total glucosides of paeony alleviate cell apoptosis and inflammation by targeting the long noncoding RNA XIST/microRNA-124-3p/ITGB1 axis in renal ischemia/reperfusion injury. Mediators Inflamm. 2020;2020:8869511. Zhang Y, Li C, Guan C, Zhou B, Wang L, Yang C, et al. MiR-181d-5p targets KLF6 to improve ischemia/reperfusion-induced AKI through effects on renal function, apoptosis, and inflammation. Front Physiol. 2020;11:510. Li D, Liu X, Li C, Zhang Y, Guan C, Huang J, et al. Role of promoting inflammation of Kruppel-like factor 6 in acute kidney injury. Ren Fail. 2020 Nov;42(1):693–703. Tan X, Zheng X, Huang Z, Lin J, Xie C, Lin Y. Involvement of S100A8/A9-TLR4-NLRP3 inflammasome pathway in contrast-induced acute kidney injury. Cell Physiol Biochem. 2017;43(1):209–22. Chen Y, Jin S, Teng X, Hu Z, Zhang Z, Qiu X, et al. Hydrogen sulfide attenuates LPS-induced acute kidney injury by inhibiting inflammation and oxidative stress. Oxid Med Cell Longev. 2018;2018:6717212. Dai XG, Li Q, Li T, Huang WB, Zeng ZH, Yang Y, et al. The interaction between C/EBPbeta and TFAM promotes acute kidney injury via regulating NLRP3 inflammasome-mediated pyroptosis. Mol Immunol. 2020 Nov;127:136–45. Zhou J, Zhang F, Lin H, Quan M, Yang Y, Lv Y, et al. The protein kinase R inhibitor C16 alleviates sepsis-induced acute kidney injury through modulation of the NF-kappaB and NLR family pyrin domain-containing 3 (NLPR3) pyroptosis signal pathways. Med Sci Monit. 2020 Oct 5;26:e926254. Jiang S, Zhang H, Li X, Yi B, Huang L, Hu Z, et al. Vitamin D/VDR attenuate cisplatin-induced AKI by down-regulating NLRP3/Caspase-1/GSDMD pyroptosis pathway. J Steroid Biochem Mol Biol. 2021 Feb;206:105789. Jia Y, Han S, Li J, Wang H, Liu J, Li N, et al. IRF8 is the target of SIRT1 for the inflammation response in macrophages. Innate Immun. 2017 Feb;23(2):188–95. Gondaliya P, Dasare A, Srivastava A, Kalia K. miR29b regulates aberrant methylation in in-vitro diabetic nephropathy model of renal proximal tubular cells. PLoS One. 2018;13(11):e0208044. Yin S, Zhang Q, Yang J, Lin W, Li Y, Chen F, et al. TGFbeta-incurred epigenetic aberrations of miRNA and DNA methyltransferase suppress Klotho and potentiate renal fibrosis. Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1207–16. Yang XH, Zhang BL, Zhang XM, Tong JD, Gu YH, Guo LL, et al. EGCG attenuates renal damage via reversing Klotho hypermethylation in diabetic db/db mice and HK-2 cells. Oxid Med Cell Longev. 2020;2020:6092715. Zhang XT, Wang G, Ye LF, Pu Y, Li RT, Liang J, et al. Baicalin reversal of DNA hypermethylation-associated Klotho suppression ameliorates renal injury in type 1 diabetic mouse model. Cell Cycle. 2020 Dec;19(23):3329–47. Salech F, Varela-Nallar L, Arredondo SB, Bustamante DB, Andaur GA, Cisneros R, et al. Local Klotho enhances neuronal progenitor proliferation in the adult hippocampus. J Gerontol A Biol Sci Med Sci. 2019 Jun 18;74(7):1043–51. Cheikhi A, Barchowsky A, Sahu A, Shinde SN, Pius A, Clemens ZJ, et al. Klotho: an elephant in aging research. J Gerontol A Biol Sci Med Sci. 2019 Jun 18;74(7):1031–42. Gomez H, Kellum JA. Sepsis-induced acute kidney injury. Curr Opin Crit Care. 2016 Dec;22(6):546–53. Brandenburger T, Salgado Somoza A, Devaux Y, Lorenzen JM. Noncoding RNAs in acute kidney injury. Kidney Int. 2018 Nov;94(5):870–81. Zhang Y, Liu Q, Liao Q. CircHIPK3: a promising cancer-related circular RNA. Am J Transl Res. 2020;12(10):6694–704. Scarfe L, Schock-Kusch D, Ressel L, Friedemann J, Shulhevich Y, Murray P, et al. Transdermal measurement of glomerular filtration rate in mice. J Vis Exp. 2018 Oct 21;(140):58520. Jang HR, Rabb H. Immune cells in experimental acute kidney injury. Nat Rev Nephrol. 2015 Feb;11(2):88–101. Fan S, Hu K, Zhang D, Liu F. Interference of circRNA HIPK3 alleviates cardiac dysfunction in lipopolysaccharide-induced mice models and apoptosis in H9C2 cardiomyocytes. Ann Transl Med. 2020 Sep;8(18):1147. Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S, et al. NAD(+) metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol. 2019 Mar;21(3):397–407. Mohamad Kamal NS, Safuan S, Shamsuddin S, Foroozandeh P. Aging of the cells: insight into cellular senescence and detection Methods. Eur J Cell Biol. 2020 Aug;99(6):151108. Terzi MY, Izmirli M, Gogebakan B. The cell fate: senescence or quiescence. Mol Biol Rep. 2016 Nov;43(11):1213–20. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016 Apr 6;7:11215. Gao M, Li H, Liu Q, Ma N, Zi P, Shi H, et al. KLF6 promotes pyroptosis of renal tubular epithelial cells in septic acute kidney injury. Shock. 2021 Oct 27;57(3):417–26. Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019 Jul 6;20(13):3328. Hutton HL, Ooi JD, Holdsworth SR, Kitching AR. The NLRP3 inflammasome in kidney disease and autoimmunity. Nephrology. 2016 Sep;21(9):736–44. Shi G, Zhang Z, Ma S, Li Y, Du S, Chu Y, et al. Hepatic interferon regulatory factor 8 expression mediates liver ischemia/reperfusion injury in mice. Biochem Pharmacol. 2021 Oct;192:114728. Deng LT, Wang QL, Yu C, Gao M. lncRNA PVT1 modulates NLRP3-mediated pyroptosis in septic acute kidney injury by targeting miR-20a-5p. Mol Med Rep. 2021 Apr;23(4):271. Jiang Y, Liu H, Yu H, Zhou Y, Zhang J, Xin W, et al. Circular RNA Calm4 regulates hypoxia-induced pulmonary arterial smooth muscle cells pyroptosis via the Circ-Calm4/miR-124-3p/PDCD6 axis. Arterioscler Thromb Vasc Biol. 2021 May 5;41(5):1675–93. Mimura S, Iwama H, Kato K, Nomura K, Kobayashi M, Yoneyama H, et al. Profile of microRNAs associated with aging in rat liver. Int J Mol Med. 2014 Oct;34(4):1065–72. Guo C, Pei L, Xiao X, Wei Q, Chen JK, Ding HF, et al. DNA methylation protects against cisplatin-induced kidney injury by regulating specific genes, including interferon regulatory factor 8. Kidney Int. 2017 Nov;92(5):1194–205. Buchanan S, Combet E, Stenvinkel P, Shiels PG. Klotho, aging, and the failing kidney. Front Endocrinol. 2020;11:560. Kale A, Sankrityayan H, Anders HJ, Gaikwad AB. Epigenetic and non-epigenetic regulation of Klotho in kidney disease. Life Sci. 2021 Jan 1;264:118644. Miao J, Huang J, Luo C, Ye H, Ling X, Wu Q, et al. Klotho retards renal fibrosis through targeting mitochondrial dysfunction and cellular senescence in renal tubular cells. Physiol Rep. 2021 Jan;9(2):e14696. Ding Y, Zheng Y, Huang J, Peng W, Chen X, Kang X, et al. UCP2 ameliorates mitochondrial dysfunction, inflammation, and oxidative stress in lipopolysaccharide-induced acute kidney injury. Int Immunopharmacol. 2019 Jun;71:336–49. Liu R, Wang SC, Li M, Ma XH, Jia XN, Bu Y, et al. An inhibitor of DRP1 (Mdivi-1) alleviates LPS-induced septic AKI by inhibiting NLRP3 inflammasome activation. Biomed Res Int. 2020;2020:2398420. Zhu H, Wang X, Wang X, Liu B, Yuan Y, Zuo X. Curcumin attenuates inflammation and cell apoptosis through regulating NF-κB and JAK2/STAT3 signaling pathway against acute kidney injury. Cell Cycle. 2020 Aug;19(15):1941–51. Article / Publication Details

First-Page Preview

Abstract of Experimental Section: Research Article

Received: November 12, 2021
Accepted: February 27, 2022
Published online: May 16, 2022

Number of Print Pages: 21
Number of Figures: 11
Number of Tables: 1

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: https://www.karger.com/GER

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif