Lactate-mediated lactylation in human health and diseases: Progress and remaining challenges

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Lactate was once considered as metabolic waste for a long time. In 2019, Professor Zhao Yingming's team from the University of Chicago found that lactate could also be used substrate to induce histone lactylation and regulate gene expression. Since then, researchers have discovered lactate-mediated play important regulatory roles in various physiological pathological processes.

Язык: Английский

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Progesterone Activates the Histone Lactylation–Hif1α-glycolysis Feedback Loop to Promote Decidualization

Endocrinology, Год журнала: 2023, Номер 165(1)

Опубликована: Ноя. 10, 2023

Decidualization is a progesterone-dependent cellular differentiation process that essential for establishing pregnancy. Robust activation of glycolysis and lactate synthesis during decidualization remarkable, but their developmental functions remain largely unknown. Herein, we identify endometrial production plays critical role in local histone lactylation, newly identified modification, important ensuring normal decidualization. Enhanced the hallmark metabolic change tightly coupled with H4K12la Inhibition lactylation impaired decidualization, either physiological conception or vivo vitro induced models. Mechanistic study based on CUT&Tag ATAC-seq revealed transcriptional factor hypoxia-inducible 1 α (Hif1α) regulatory target H4K12la, turn forms an H4K12la-Hif1α-glycolysis feedback loop to drive Moreover, demonstrate directly activated by progesterone Our not only advances current knowledge regulating uterine function, also establishes novel functional link among major endocrine factors, change, epigenetic modification remodeling. These findings present valuable clues develop clinical intervention strategies improve pregnancy outcomes following both natural assisted reproduction.

Язык: Английский

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SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101563 - 101563

Опубликована: Фев. 1, 2025

Bone morphogenetic protein 9 (BMP9) exhibits remarkable osteogenic potential. However, the intricate mechanisms driving this function of BMP9 remain elusive. This study endeavors to investigate potential role sirtuin 5 (SIRT5) in enhancing BMP9's capacity and decipher underlying molecular pathways. To achieve aim, we employed real-time PCR, western blotting, histochemical staining, a cranial defect repair model assess impact SIRT5 on BMP9-mediated osteogenesis. We utilized immunofluorescent immunoprecipitation assay explore associated mechanisms. Our results revealed that significantly up-regulated BMP9-induced markers, while knockdown reduced their expression. Concurrently, hypoxia-inducible factor 1 subunit alpha (HIF-1α) level was increased by SIRT5, but knockdown. Notably, HIF-1α potentiated SIRT5's ability strengthen potential, whereas silencing effect, which confirmed bone assay. The acetylation malonylation levels were may enhance its stability promote effect. Conversely, reversed these effects promoted degradation HIF-1α. Collectively, our demonstrated could be potentially through stabilizing reducing modification. discovery offer novel strategy accelerate tissue engineering differentiation, it also sheds light possible differentiation.

Язык: Английский

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The role of lactate metabolism and lactylation in pulmonary arterial hypertension

Respiratory Research, Год журнала: 2025, Номер 26(1)

Опубликована: Март 12, 2025

Pulmonary arterial hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary artery pressure vascular remodeling. Recent studies have underscored the pivotal role of metabolic dysregulation epigenetic modifications in pathogenesis PAH. Lactate, byproduct glycolysis, now recognized as key molecule that links cellular metabolism with activity regulation. findings indicate that, addition to altered glycolytic dysregulated. Lactate homeostasis lactylation—a novel modification—also play significant development This review synthesizes current knowledge regarding relationship between PAH, particular focus on cumulative effects lactate cells. Furthermore, lactylation, an emerging modification, discussed context By elucidating interplay lactylation this aims provide insights into potential therapeutic targets. Understanding these pathways may lead innovative strategies for managing PAH improving patient outcomes. Future research should underlying mechanisms through which influences pathophysiology thereby aiding targeted interventions.

Язык: Английский

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Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases

Journal of Physiology and Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Язык: Английский

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