LncRNA KCNQ1OT1 (potassium Voltage-gated Channel Subfamily Q Member 1 Opposite Strand/antisense Transcript 1) Aggravates Acute Kidney Injury by Activating P38/NF-κB Pathway Via MiR-212-3p/MAPK1 (mitogen-activated Protein Kinase 1) Axis in Sepsis

Overview

Journal Bioengineered

Date 2021 Nov 16

PMID 34783627

Citations 9

Authors

Haixia Wang

Hongbin Mou

Xiaolan Xu

Changhua Liu

Gang Zhou

Bo Gao

Affiliations

Soon will be listed here.

Abstract

Acute kidney injury (AKI), a common complication of sepsis, is characterized by a rapid loss of renal excretory function. A variety of etiologies and pathophysiological processes may contribute to AKI. Previously, mitogen-activated protein kinase 1 (MAPK1) was reported to regulate cellular processes in various sepsis-associated diseases. The current study aimed to further explore the biological function and regulatory mechanism of MAPK1 in sepsis-induced AKI. In our study, MAPK1 exhibited high expression in the serum of AKI patients. Functionally, knockdown of MAPK1 suppressed inflammatory response, cell apoptosis in response of lipopolysaccharide (LPS) induction in HK-2 cells. Moreover, MAPK1 deficiency alleviated renal inflammation, renal dysfunction, and renal injury . Mechanistically, MAPK1 could activate the downstream p38/NF-κB pathway. Moreover, long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) was identified to serve as a competing endogenous RNA for miR-212-3p to regulate MAPK1. Finally, rescue assays indicated that the inhibitory effect of KCNQ1OT1 knockdown on inflammatory response, cell apoptosis, and p38/NF-κB pathway was reversed by MAPK1 overexpression in HK-2 cells. In conclusion, KCNQ1OT1 aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 axis in sepsis. Therefore, KCNQ1OT may serve as a potential biomarker for the prognosis and diagnosis of AKI patients.

Citing Articles

Kidney Injury: Focus on Molecular Signaling Pathways.

Liu W, Hu M, Wang L, Mirzaei H Curr Med Chem. 2024; 31(28):4510-4533.

PMID: 38314680 DOI: 10.2174/0109298673271547231108060805.

Unveiling the mechanisms of nephrotoxicity caused by nephrotoxic compounds using toxicological network analysis.

Xi K, Zhang M, Li M, Tang Q, Zhao Q, Chen W Mol Ther Nucleic Acids. 2023; 34:102075.

PMID: 38074898 PMC: 10709196. DOI: 10.1016/j.omtn.2023.102075.

Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis.

Wang T, Xu S, Zhang L, Yang T, Fan X, Zhu C BMC Genomics. 2023; 24(1):484.

PMID: 37620751 PMC: 10464037. DOI: 10.1186/s12864-023-09535-7.

Silencing LncRNA SNHG16 suppresses the diabetic inflammatory response by targeting the miR-212-3p/NF-κB signaling pathway.

Huang L, Xiong S, Liu H, Zhang R, Wu Y, Hu X Diabetol Metab Syndr. 2023; 15(1):119.

PMID: 37280692 PMC: 10245462. DOI: 10.1186/s13098-023-01070-5.

Epigenetic dysregulation of autophagy in sepsis-induced acute kidney injury: the underlying mechanisms for renoprotection.

Zhao S, Liao J, Shen M, Li X, Wu M Front Immunol. 2023; 14:1180866.

PMID: 37215112 PMC: 10196246. DOI: 10.3389/fimmu.2023.1180866.

References

Tafrihi M, Hasheminasab E . MiRNAs: Biology, Biogenesis, their Web-based Tools, and Databases. Microrna. 2018; 8(1):4-27. DOI: 10.2174/2211536607666180827111633. View

Wang Y, Tan J, Xu C, Wu H, Zhang Y, Xiong Y . Identification and construction of lncRNA-associated ceRNA network in diabetic kidney disease. Medicine (Baltimore). 2021; 100(22):e26062. PMC: 8183707. DOI: 10.1097/MD.0000000000026062. View

Liu Y, Zhang X, Li X, Tang Y, Zhao X . miR-212-3p reduced proliferation, and promoted apoptosis of fibroblast-like synoviocytes via down-regulating SOX5 in rheumatoid arthritis. Eur Rev Med Pharmacol Sci. 2018; 22(2):461-471. DOI: 10.26355/eurrev_201801_14196. View

Verma V, Malik S, Narayanan S, Mutneja E, Sahu A, Bhatia J . Role of MAPK/NF-κB pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats. Mol Biol Rep. 2019; 46(1):1139-1148. DOI: 10.1007/s11033-018-04575-9. View

Zhao D, Liu Z, Zhang H . The protective effect of the TUG1/miR‑197/MAPK1 axis on lipopolysaccharide‑induced podocyte injury. Mol Med Rep. 2019; 20(1):49-56. DOI: 10.3892/mmr.2019.10216. View

Zuo Q, Shi M, Chen J, Liao W . The Ras signaling pathway mediates cetuximab resistance in nasopharyngeal carcinoma. Biomed Pharmacother. 2011; 65(3):168-74. DOI: 10.1016/j.biopha.2011.02.005. View

Srivastava S, Hedayat A, Kanasaki K, Goodwin J . microRNA Crosstalk Influences Epithelial-to-Mesenchymal, Endothelial-to-Mesenchymal, and Macrophage-to-Mesenchymal Transitions in the Kidney. Front Pharmacol. 2019; 10:904. PMC: 6707424. DOI: 10.3389/fphar.2019.00904. View

Kane-Gill S, Meersch M, Bell M . Biomarker-guided management of acute kidney injury. Curr Opin Crit Care. 2020; 26(6):556-562. DOI: 10.1097/MCC.0000000000000777. View

Lin J, Zheng Y, Zhang Z, Shen W, Li X, Wei T . Suppression of Endothelial-to-Mesenchymal Transition by SIRT (Sirtuin) 3 Alleviated the Development of Hypertensive Renal Injury. Hypertension. 2018; 72(2):350-360. DOI: 10.1161/HYPERTENSIONAHA.118.10482. View

10.

Yu X, Cui L, Hou F, Liu X, Wang Y, Wen Y . Angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axis prevents pancreatic acinar cell inflammatory response via inhibition of the p38 mitogen-activated protein kinase/nuclear factor-κB pathway. Int J Mol Med. 2017; 41(1):409-420. DOI: 10.3892/ijmm.2017.3252. View

11.

Chen F, Zheng L, Wu D, Gong H, Cen H, Chen W . [Regulatory relationship between lncRNA KCNQ1OT1 and miR-146a-3p in preeclampsia]. Zhonghua Fu Chan Ke Za Zhi. 2020; 55(8):535-543. DOI: 10.3760/cma.j.cn112141-20200322-00246. View

12.

Poston J, Koyner J . Sepsis associated acute kidney injury. BMJ. 2019; 364:k4891. PMC: 6890472. DOI: 10.1136/bmj.k4891. View

13.

Wang J, Song J, Li Y, Shao J, Xie Z, Sun K . Down-regulation of LncRNA CRNDE aggravates kidney injury via increasing MiR-181a-5p in sepsis. Int Immunopharmacol. 2019; 79:105933. DOI: 10.1016/j.intimp.2019.105933. View

14.

Zyuzkov G, Zhdanov V, Udut E, Miroshnichenko L, Polyakova T, Stavrova L . Peculiarities of Intracellular Signal Transduction in the Regulation of Functions of Mesenchymal, Neural, and Hematopoietic Progenitor Cells. Bull Exp Biol Med. 2019; 167(2):201-206. DOI: 10.1007/s10517-019-04491-3. View

15.

Nandikanti D, Gosmanova E, Gosmanov A . Acute Kidney Injury Associated with Linagliptin. Case Rep Endocrinol. 2016; 2016:5695641. PMC: 4769737. DOI: 10.1155/2016/5695641. View

16.

Tang T, Lv L, Wang B, Cao J, Feng Y, Li Z . Employing Macrophage-Derived Microvesicle for Kidney-Targeted Delivery of Dexamethasone: An Efficient Therapeutic Strategy against Renal Inflammation and Fibrosis. Theranostics. 2019; 9(16):4740-4755. PMC: 6643445. DOI: 10.7150/thno.33520. View

17.

Zhu P, Ren M, Yang C, Hu Y, Ran J, Yan L . Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes. Exp Dermatol. 2012; 21(2):123-9. DOI: 10.1111/j.1600-0625.2011.01408.x. View

18.

Liu X, Zhu N, Zhang B, Xu S . Long Noncoding RNA TCONS_00016406 Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Regulating the miR-687/PTEN Pathway. Front Physiol. 2020; 11:622. PMC: 7325890. DOI: 10.3389/fphys.2020.00622. View

19.

Yu L, Yang J . MiR-29 increases apoptosis of retinal ganglion cells in rat glaucoma model through AKT signaling pathway. Panminerva Med. 2019; 63(1):90-91. DOI: 10.23736/S0031-0808.19.03670-X. View

20.

Morigi M, Perico L, Rota C, Longaretti L, Conti S, Rottoli D . Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury. J Clin Invest. 2015; 125(2):715-26. PMC: 4319434. DOI: 10.1172/JCI77632. View