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Mechanism of KMT2D-mediated epigenetic modification in IL-1β-induced nucleus pulposus cell degeneration

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dc.contributor.authorLiu, Hongjiang
dc.contributor.authorLiu, Haiquan
dc.contributor.authorMeng, Zuyu
dc.contributor.authorZhang, Wensheng
dc.date.accessioned2025-05-05T15:38:11Z
dc.date.available2025-05-05T15:38:11Z
dc.date.issued2025
dc.description.abstractBackground. Intervertebral disc (IVD) degeneration (IVDD) is characterized by structural destruction accompanied by accelerated signs of aging. This study aimed to investigate the mechanism of lysine methyltransferase 2D (KMT2D) in the proliferation, apoptosis, and inflammation of nucleus pulposus cells (NPCs) in IVDD. Methods. Mouse-derived NPCs were cultured and induced with interleukin-1 beta (IL-1β) to establish cell models. KMT2D expression was detected by western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). KMT2D expression was interfered with, and the contents of IL-18, IL-6, and tumor necrosis factor (TNF) were detected by enzyme-linked immunosorbent assay. Cell proliferation, apoptosis, and the expression of miR-133a-5p and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) were measured. The enrichment of KMT2D and Histone 3 Lysine 4 monomethylation/dimethylation (H3K4me1/2) on the miR-133a-5p promoter was analyzed by chromatin immunoprecipitation and qPCR. The binding of miR-133a-5p and PFKFB2 was analyzed by a dual-luciferase assay. Results. IL-1β treatment promoted KMT2D expression in NPCs. KMT2D knockdown reduced inflammation and apoptosis and promoted the proliferation of IL-1β-induced NPCs. Mechanistically, KMT2D upregulated miR-133a-5p expression by increasing the level of H3K4me2 at the miR-133a-5p promoter, thereby promoting the binding between miR-133a-5p and PFKFB2 and downregulating the transcription of PFKFB2. miR-133a-5p overexpression or PFKFB2 knockdown alleviated the protective effect of KMT2D knockdown on IL-1β-induced NPCs. Conclusion. KMT2D promoted miR-133a-5p expression through H3K4me2 methylation, thereby promoting the binding of miR-133a-5p to PFKFB2, reducing the mRNA level of PFKFB2, promoting inflammation and apoptosis of IL-1β-induced NPCs, and inhibiting NPC proliferation.es
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dc.format.extent11es
dc.identifier.citationHistology and Histopathology Vol. 40, nº05 (2025)
dc.identifier.doihttps://doi.org/10.14670/HH-18-813
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/153946
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectIntervertebral disc degenerationes
dc.subjectNucleus pulposus cellses
dc.subjectKMT2Des
dc.subjectmiR-133a-5pes
dc.subjectPFKFB2es
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleMechanism of KMT2D-mediated epigenetic modification in IL-1β-induced nucleus pulposus cell degenerationes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.40, nº5 (2025)