ENO3 regulates ferroptosis by interaction with PKM2 to promote the progression of metabolic dysfunction-associated steatotic liver disease

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dc.contributor.authorQian Hao
dc.contributor.authorXue Li
dc.contributor.authorJing Liu
dc.contributor.authorMinghao Li
dc.contributor.authorBaoding Li
dc.contributor.authorShengjuan Hu
dc.contributor.authorYanling Li
dc.contributor.authorXiaofei Li
dc.contributor.authorYuanyuan Tang
dc.contributor.authorFuliang Pan
dc.contributor.authorYanxia Liu
dc.contributor.authorMin Niu
dc.contributor.authorZhenzi Cao
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2025-12-19T12:12:53Z
dc.date.available2025-12-19T12:12:53Z
dc.date.issued2026
dc.description.abstractBackground. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive lipid accumulation in the liver. The glycolytic enzyme enolase 3 (ENO3) is reported to be most significantly elevated in the analysis of MASLD-related sequencing results based on the GEO database. However, the specific mechanism by which ENO3 regulates MASLD is not fully understood. Objective. To investigate the role and possible molecular mechanism of ENO3 in MASLD. Methods. The expression of ENO3 and PKM2 in the liver tissues of control and MASLD rats was detected by immunohistochemistry and western blot. In vitro studies involved treating THLE-2 cells with free fatty acids (FFA) and Ferrostatin-1 (Fer-1), as well as manipulating ENO3 expression via small interfering RNA (siRNA) and overexpression plasmids, and manipulating PKM2 expression via siRNA. Fat accumulation was assessed using Oil Red O staining and measurements of intracellular total cholesterol (TC) and triglycerides (TG). Ferroptosis markers, including SLC7A11, GPX4, Fe2+, and malondialdehyde (MDA), were evaluated. Protein-protein interactions between ENO3 and PKM2 were examined using co-immunoprecipitation (Co-IP) and immunofluorescence. Results. MASLD liver tissues exhibited significantly higher levels of ENO3 and PKM2. Silencing ENO3 in FFA-treated THLE-2 cells reduced fat accumulation, downregulated PKM2 expression, and decreased ferroptosis markers. Conversely, ENO3 overexpression promoted fat accumulation and ferroptosis, which were mitigated by Fer-1 or si-PKM2. Co-IP and immuno-fluorescence confirmed the physical interaction and co-localization of ENO3 and PKM2 in THLE-2 cells. Conclusions. ENO3 interacted with PKM2 to regulate ferroptosis and further promoted the progression of MASLD.
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dc.format.extent13
dc.identifier.doihttps://doi.org/10.14670/HH-18-933
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/181749
dc.languageeng
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologia
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.subjectPKM2
dc.subjectFerroptosis
dc.subjectMetabolic dysfunction-associated steatotic liver disease (MASLD)
dc.subjectFat accumulation
dc.subjectENO3
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleENO3 regulates ferroptosis by interaction with PKM2 to promote the progression of metabolic dysfunction-associated steatotic liver disease
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.41, Nº1, (2026)