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已发表论文
METTL3 对 MALAT1 的 m6A 修饰促进小鼠脓毒症诱导的急性肾损伤中的细胞焦亡和炎症反应
Authors Guo P, Deng G, Li L, Wei H, Gong Y, Tan Y, Ma Y
Received 24 March 2025
Accepted for publication 29 September 2025
Published 24 October 2025 Volume 2025:18 Pages 14663—14678
DOI https://doi.org/10.2147/JIR.S530214
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Wenjian Li
Pengwei Guo,1,* Gao Deng,1,* Lingling Li,1 Haidong Wei,1 Yunxia Gong,1 Yanhong Tan,1 Yanfei Ma2
1Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Glandular Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China
*These authors have contributed equally to this work
Correspondence: Yanfei Ma, Department of Glandular Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2nd Road, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email yanfei.ma@ymun.edu.cn
Background: Sepsis-induced acute kidney injury (SAKI) significantly contributes to renal dysfunction. Long non-coding RNA MALAT1 has been implicated in regulating inflammation and cell death in various diseases. However, its role in SAKI and the underlying mechanisms remain unclear.
Methods: A lipopolysaccharide (LPS)-induced SAKI mouse model and LPS-treated TCMK-1 cells were established. METTL3 and MALAT1 were manipulated via lentiviral-mediated knockdown or overexpression. m6A RNA levels were measured using MeRIP-qPCR, while pyroptosis and inflammation were assessed through ELISA, flow cytometry, Western blotting, immunohistochemistry, and immunofluorescence. RNA immunoprecipitation was conducted to confirm the interaction between METTL3 and MALAT1.
Results: LPS treatment significantly increased METTL3 and MALAT1 expression and enhanced m6A modification of MALAT1. METTL3 knockdown reduced pyroptosis markers (cleaved GSDMD, Caspase-1, and NLRP3) and inflammatory cytokines (IL-1β and IL-18), while MALAT1 overexpression partially reversed these effects. RIP confirmed that METTL3 binds directly to MALAT1. In vivo and in vitro experiments demonstrated that the METTL3/MALAT1 axis contributes to pyroptosis in SAKI.
Conclusion: METTL3 promotes pyroptosis in SAKI by enhancing the m6A modification of MALAT1. Targeting the METTL3/MALAT1 axis may provide a potential therapeutic strategy for SAKI by mitigating renal inflammation and cell death.
Keywords: sepsis-induced acute kidney injury, METTL3, MALAT1, pyroptosis
1Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Glandular Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China
*These authors have contributed equally to this work
Correspondence: Yanfei Ma, Department of Glandular Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan 2nd Road, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email yanfei.ma@ymun.edu.cn
Background: Sepsis-induced acute kidney injury (SAKI) significantly contributes to renal dysfunction. Long non-coding RNA MALAT1 has been implicated in regulating inflammation and cell death in various diseases. However, its role in SAKI and the underlying mechanisms remain unclear.
Methods: A lipopolysaccharide (LPS)-induced SAKI mouse model and LPS-treated TCMK-1 cells were established. METTL3 and MALAT1 were manipulated via lentiviral-mediated knockdown or overexpression. m6A RNA levels were measured using MeRIP-qPCR, while pyroptosis and inflammation were assessed through ELISA, flow cytometry, Western blotting, immunohistochemistry, and immunofluorescence. RNA immunoprecipitation was conducted to confirm the interaction between METTL3 and MALAT1.
Results: LPS treatment significantly increased METTL3 and MALAT1 expression and enhanced m6A modification of MALAT1. METTL3 knockdown reduced pyroptosis markers (cleaved GSDMD, Caspase-1, and NLRP3) and inflammatory cytokines (IL-1β and IL-18), while MALAT1 overexpression partially reversed these effects. RIP confirmed that METTL3 binds directly to MALAT1. In vivo and in vitro experiments demonstrated that the METTL3/MALAT1 axis contributes to pyroptosis in SAKI.
Conclusion: METTL3 promotes pyroptosis in SAKI by enhancing the m6A modification of MALAT1. Targeting the METTL3/MALAT1 axis may provide a potential therapeutic strategy for SAKI by mitigating renal inflammation and cell death.
Keywords: sepsis-induced acute kidney injury, METTL3, MALAT1, pyroptosis