Ask about this productRelated genes to: JMJD2A antibody
- Gene:
- KDM4A NIH gene
- Name:
- lysine demethylase 4A
- Previous symbol:
- JMJD2, JMJD2A
- Synonyms:
- KIAA0677, JHDM3A, TDRD14A
- Chromosome:
- 1p34.2-p34.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-08-08
- Date modifiied:
- 2018-02-13
Related products to: JMJD2A antibody
Related articles to: JMJD2A antibody
- Idiopathic pulmonary fibrosis is a progressive and fatal disorder characterized by abnormal activation of alveolar fibroblasts. However, the metabolic reprogramming of alveolar fibroblasts during lung injury remains unclear. Here we show that uptake of branched-chain amino acids is increased, whereas their catabolism is significantly impaired in fibrotic lung fibroblasts and mouse lung tissues. Branched-chain amino acids promote lung fibroblast activation and bleomycin-induced lung fibrosis. Genetic inactivation of branched-chain amino acid transaminase 2 exacerbates fibrosis, whereas inhibition of the corresponding transporter SLC7A5 or enhancement of catabolism attenuates pulmonary fibrosis in male mice. Mechanistically, ATF4 and PPARγ regulate the expression of SLC7A5 and BCAA catabolic genes, respectively. We identify KDM4A as a key mediator of the epigenetic regulation of fibrotic genes. Notably, dysregulated BCAA metabolism is associated with disease severity in patients, suggesting that targeting BCAA metabolism may serve as a promising therapeutic strategy for idiopathic pulmonary fibrosis. - Source: PubMed
Publication date: 2026/04/27
Yao JieFang SuLei MiaoOu ZexianZeng ChuanfeiPeng WanliHe NaYang LianGuo BingpengFang MingmengWang CuihuaLv JieWu ShuangZhang Wei KevinHuang HuiminPeng YangRao WeiRong ZhiliYang PenghuiWang ChaoqunHan QianHu Wenxiang - The effectiveness of treatment of head and neck squamous cell carcinomas (HNSCC) is still unsatisfactory, and novel therapeutics could improve outcomes. Histone deacetylases (HDAC) and histone lysine demethylases (KDMs) emerged as important molecular targets in HNSCC. Moreover, joint inhibition of epigenetic targets may be therapeutically advantageous. Thus, the aim of this project was to evaluate the effects of combinations of panobinostat, a pan-HDAC inhibitor, with KDM4-6 inhibitors (KDMi), ML324, GSK-J4, and JIB-04. Experiments were performed in FaDu and SCC-152 cell lines. Resazurin and clonogenic assays were used to evaluate the cell viability and clonogenic potential, respectively. Apoptosis was assessed by flow cytometry after Annexin V staining. Flow-cytometric detection of γH2A.X was applied for DNA damage evaluation. Gene expression was quantified by qPCR. KDM proteins occupancy at gene promoters was measured by quantitative chromatin immunoprecipitation. KDMi enhanced the anticancer effects of panobinostat in HNSCC cell lines. The combinations of panobinostat with ML324 and JIB-04 synergistically reduced cell viability in FaDu and SCC-152 cells, and increased apoptosis induction in SCC-152 cells. These effects could be attributed to the modulation of BIRC5 and CDKN2A expression, and enhanced accumulation of DNA double-strand breaks following combinatorial treatments in FaDu cells. Decreased expression of stemness-related genes upon KDMi treatment in FaDu cells was associated with decreased binding of KDM4A and/or KDM6B at SOX2 and POU5F1 gene promoters. The suppression of stemness-associated phenotype, and the concurrent promotion of apoptosis by the studied combinations of chemicals, suggest their potential as a novel therapeutic strategy in HNSCC. - Source: PubMed
Publication date: 2026/04/20
Dorna DawidKleszcz RobertDrabarz KarolinaKubiak MałgorzataStefanska BarbaraPaluszczak Jarosław - Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, which can cause various complications that threaten health. Long non-coding RNA (lncRNA) is associated with the occurrence and development of diabetes and its complications. - Source: PubMed
Publication date: 2026/04/03
Zeng YanSun LiyuLi JunliHuang ZhongyunYin Pengying - Metabolic adaptations that fuel metastatic dissemination are increasingly mapped, yet the existence of intrinsic metabolic "brakes" that actively restrain metastatic progression remains enigmatic. Here, we unveil bisphosphoglycerate mutase (BPGM) as a previously unrecognized metastasis suppressor that orchestrates a phospho-epigenetic relay linking glycolytic flux to carnitine-dependent fatty acid oxidation. Through high-resolution metabolomics, we discover that BPGM and its catalytic product 2,3-bisphosphoglycerate (2,3-BPG) constitute a metabolic checkpoint whose disruption predicts metastatic virulence in multiple cancers. Mechanistically, BPGM suppresses metastasis by triggering CDK1-T phosphorylation-dependent assembly of an EZH2-H3K27me3 repressor complex that silences γ-butyrobetaine hydroxylase (BBOX1), the rate-limiting enzyme in carnitine biosynthesis. This phospho-switch mechanism converts glycolytic 2,3-BPG levels into epigenetic orchestrator, thereby starving metastatic cells of carnitine-required fatty acid oxidation. Hypoxia-mediated KDM4A-H3K9me3 cascade emerges as the upstream inactivator of this metabolic-epigenetic checkpoint, explaining how tumor microenvironmental stress liberates metastatic potential. Therapeutically, pharmacological BBOX1 inhibition with Meldonium recapitulates BPGM-mediated metastasis suppression in orthotopic models, reducing metastatic burden. These findings reveal BPGM as a metabolic gatekeeper that integrates bioenergetic sensing with chromatin remodeling to constrain metastatic competence, while hypoxia-mediated checkpoint failure unleashes carnitine-fueled metastatic progression. Targeting the hypoxia-BPGM-BBOX1 axis represents an innovative approach for metastasis-preventive therapy. - Source: PubMed
Publication date: 2026/03/23
Wu Meng-ZhiFeng DouLiu Wu-PingHuang Wei-LunWu QiangChou Tian-ShengXiao Wen-HaoYao Zhou-ZhouLi Zhen-JiangXie Ting-TingChen Chang-HanYang Zhi-YuMao Rui-WenWu Ci-ChunWang Jun-ChengZhang Yu-JinKellems Rodney EXia Yang - Osteoarthritis (OA)-associated pain, driven by M1 macrophage polarization and inflammation, lacks effective therapies. Tetrahydropalmatine (THP), known for its anti-inflammatory and analgesic properties, was evaluated for its effects on OA-induced pain and macrophage polarization. A destabilization of the medial meniscus (DMM)-induced OA mouse model and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were used. Behavioral tests, histology, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting (WB), and immunohistochemistry (IHC) were used to assess pain, inflammation, and the expression of lysine demethylase 4A (KDM4A), murine double minute 2 (MDM2), and hypoxia-inducible factor-1α (HIF-1α). THP treatment alleviated OA-induced pain and cartilage damage and reduced CD86 expression, and reduced the expression of pro-inflammatory factors tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and key signaling molecules (KDM4A, MDM2, and HIF-1α). Mechanistically, KDM4A directly bound to the MDM2 promoter and activated its transcription via H3K9me3 demethylation, whereas MDM2 enhanced HIF-1α signaling to promote M1 polarization. Overexpression of KDM4A reversed the inhibitory effects of THP on MDM2/HIF-1α signaling and inflammation. These findings indicate that THP mitigates OA-associated pain and inflammation by blocking KDM4A-mediated MDM2 transcription and suppressing HIF-1α-dependent M1 macrophage polarization, highlighting the KDM4A-MDM2-HIF-1α axis as a potential therapeutic target. - Source: PubMed
Chen XiaoboSun XiaoyongZhong QiumingGan HongxiaLv WeipingYang Ying