p38 MAPK and MKP-1 control the glycolytic program via the bifunctional glycolysis regulator PFKFB3 during sepsis

Mager, Carli E; Mormol, Justin M.; Shelton, Evan D.; Murphy, Parker R.; Bowman, Bridget; Barley, Timothy J.; Wang, Xiantao; Liu, Kevin; Nelin, Leif D.; Hafner, Markus; Liu, Yusen

doi:10.1016/j.jbc.2023.103043

Cited by 9 publications

(4 citation statements)

References 67 publications

(99 reference statements)

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“…This finding implies that as reprogramming progresses, the expression of these genes increases gradually, facilitated by Dux and linked to the metabolism pathway in iPSCs development. We analyzed public data and used KEGG to find that genes enriched in Dux in ESC are also enriched in MAPK and HIF-1 signaling pathways, whereas the p38 MAPK pathway could enhance glycolysis ( 33 ), and the HIF-1/LDH pathway could promote lactate production ( 34 ), suggesting a link between Dux and glycolysis ( Supplementary Figure 1E ). Heatmap showed the expression level of glycolysis-related genes in Dux D4 and D4 groups (gene set was downloaded from REACTOME [REACTOME_GLYCOLYSIS, R-MMU-70171]), Log 2 (FPKM + 1) matrix was used as input, and scaled by rows.…”

Section: Resultsmentioning

confidence: 99%

Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader

Hu,

Huang,

Yang

et al. 2024

Nucleic Acids Research

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The process of induced pluripotent stem cells (iPSCs) reprogramming involves several crucial events, including the mesenchymal-epithelial transition (MET), activation of pluripotent genes, metabolic reprogramming, and epigenetic rewiring. Although these events intricately interact and influence each other, the specific element that regulates the reprogramming network remains unclear. Dux, a factor known to promote totipotency during the transition from embryonic stem cells (ESC) to 2C-like ESC (2CLC), has not been extensively studied in the context of iPSC reprogramming. In this study, we demonstrate that the modification of H3K18la induced by Dux overexpression controls the metabolism-H3K18la-MET network, enhancing the efficiency of iPSC reprogramming through a metabolic switch and the recruitment of p300 via its C-terminal domain. Furthermore, our proteomic analysis of H3K18la immunoprecipitation experiment uncovers the specific recruitment of Brg1 during reprogramming, with both H3K18la and Brg1 being enriched on the promoters of genes associated with pluripotency and epithelial junction. In summary, our study has demonstrated the significant role of Dux-induced H3K18la in the early reprogramming process, highlighting its function as a potent trigger. Additionally, our research has revealed, for the first time, the binding of Brg1 to H3K18la, indicating its role as a reader of histone lactylation.

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Section: Resultsmentioning

confidence: 99%

Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader

Hu,

Huang,

Yang

et al. 2024

Nucleic Acids Research

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“…Mager CE et al. found that MKP-1 defects mediate increased PFKFB3 expression via the p38 MAPK pathway in both an E. coli-infected mouse model of sepsis and an LPS-stimulated macrophage model, leading to upregulation of macrophage glycolysis and the development of sepsis ( 49 ). The rate-limiting enzyme of glycolysis, pyruvate kinase (PK), catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate.…”

Section: Relevant Metabolic Reprogramming Of Macrophagementioning

confidence: 99%

“…Schilperoort M et al found that the PFKFB2-mediated glycolytic pathway is rapidly activated in macrophages after phagocytosis and that the lactate it produces promotes the expression of the efferocytosis receptors MerTK and LRP1 via calcium signaling, thereby driving sustained phagocytosis (48). Mager CE et al found that MKP-1 defects mediate increased PFKFB3 expression via the p38 MAPK pathway in both an E. coli-infected mouse model of sepsis and an LPS-stimulated macrophage model, leading to upregulation of macrophage glycolysis and the development of sepsis (49). The rate-limiting enzyme of glycolysis, pyruvate kinase (PK), catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate.…”

Section: Glycolysis and Oxidative Phosphorylationmentioning

confidence: 99%

Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues

Xu,

Liu,

et al. 2024

Front. Immunol.

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It is commonly known that different macrophage phenotypes play specific roles in different pathophysiological processes. In recent years, many studies have linked the phenotypes of macrophages to their characteristics in different metabolic pathways, suggesting that macrophages can perform different functions through metabolic reprogramming. It is now gradually recognized that lactate, previously overlooked as a byproduct of glycolytic metabolism, acts as a signaling molecule in regulating multiple biological processes, including immunological responses and metabolism. Recently, lactate has been found to mediate epigenetic changes in macrophages through a newfound lactylation modification, thereby regulating their phenotypic transformation. This novel finding highlights the significant role of lactate metabolism in macrophage function. In this review, we summarize the features of relevant metabolic reprogramming in macrophages and the role of lactate metabolism therein. We also review the progress of research on the regulation of macrophage metabolic reprogramming by lactylation through epigenetic mechanisms.

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“…PFKFB3被发现不仅在癌细胞中表达升高, 而且在脂多糖或缺氧处理的上皮细胞和巨噬细胞等多种细胞类型中明显上调, 介导脓毒血症及髓性白血病等疾病的发生 [42,43] . PFKFB4主要发挥调节糖酵解, 将葡萄糖代谢中间体转移到磷酸戊糖途径(PPP), 发挥管理活性氧 (ROS)积累的作用.…”

Section: 葡萄糖代谢重编程(有氧糖酵解)unclassified

RNA methylation, metabolic reprogramming and pulmonary hypertension

Hu,

Shen,

Gan

et al. 2023

Chin. Sci. Bull.

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p38 MAPK and MKP-1 control the glycolytic program via the bifunctional glycolysis regulator PFKFB3 during sepsis

Cited by 9 publications

References 67 publications

Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader

Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader

Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues

RNA methylation, metabolic reprogramming and pulmonary hypertension

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