METTL1 aggravates sepsis-acute kidney injury by promoting m7G methylation of NLRP3-mediated pyroptosis

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dc.contributor.authorYuexuan Chen
dc.contributor.authorMing Fang
dc.contributor.authorJingjing Hu
dc.contributor.authorLu Wang
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2025-11-11T09:00:40Z
dc.date.available2025-11-11T09:00:40Z
dc.date.issued2025
dc.description.abstractSepsis is a major cause of acute kidney injury (AKI). Dysregulation of N7-methyladenosine (m7G) methylation is a pathogenic mechanism of sepsis. However, the role of m7G methylation in renal damage remains poorly understood. In this study, we investigated the regulation of METTL1, an m7G "writer", on pyroptosis in sepsis-induced AKI. HK-2 cells were treated with lipopolysaccharide (LPS), and pyroptosis was assessed using enzyme-linked immunosorbent assays and western blotting. The m7G methylation status of NLRP3 was analyzed through methylated-RNA immunoprecipitation (Me-RIP), RNA immuno-precipitation (RIP), and dual-luciferase reporter assays. Renal injury in mice subjected to cecal ligation and puncture (CLP) was evaluated using hematoxylin and eosin (H&E) staining. Our results demonstrated that METTL1 expression was significantly upregulated in both LPS-treated HK-2 cells and the CLP-induced mouse model. Interfering with METTL1 suppressed LPS-induced pyroptosis in vitro and attenuated kidney damage and pyroptosis in vivo. Furthermore, METTL1 knockdown inhibited m7G methylation of NLRP3, thereby reducing its stability. Overexpression of NLRP3 abrogated the inhibition of pyroptosis caused by METTL1 knockdown. In conclusion, silencing of METTL1 alleviates sepsis-induced AKI by inhibiting m7G methylated NLRP3-mediated pyroptosis in renal tubular epithelial cells. These findings suggest that targeting METTL1 may represent a promising therapeutic strategy for managing sepsis-associated AKI.
dc.formatapplication/pdf
dc.format.extent10
dc.identifier.doihttps://doi.org/10.14670/HH-18-910
dc.identifier.eissn0213-3911
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/172149
dc.languageeng
dc.relationSin financiacion externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectKidney injury
dc.subjectm7G methylation
dc.subjectMETTL1
dc.subjectPyroptosis
dc.subjectNLRP3
dc.subjectSepsis
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleMETTL1 aggravates sepsis-acute kidney injury by promoting m7G methylation of NLRP3-mediated pyroptosis
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.40, Nº12, (2025)