H3K18 Lactylation-Mediated CHI3L1 Expression Exacerbates Diabetic Arterial Calcification DOI
Yi Zhu, Jiali Zhang, Fangfang Wang

et al.

Published: Jan. 1, 2024

Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation lactate the microenvironment can promote VSMC calcification diabetes, although specific mechanism remains to be fully elucidated. Lactate participates lactylation as a substrate and plays role many diseases. In this study, we explored characteristics diabetic arterial underlying molecular mechanism. We found that high-glucose calcified VSMC, overall level was significantly increased. Mass spectrometry analysis revealed significant upregulation H3 histone lactylation. After site-specific point-mutation (lysine-to-arginine) at K18 simulate delactylation modification, reduced. Through combination H3K18la ChIP-seq, RNA-seq, ChIP-qPCR experiments, confirmed upregulate CHI3L1. generated CHI3L1 knockdown VSMCs constructed mouse model by knockout whole gene. alleviated osteogenic phenotype transformation calcification. RNA-seq downstream signaling showed activates IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition IL-13Ra2 reduced conclude environment, site undergoes modification VSMCs, upregulating CHI3L1, which turn regulates pathway, ultimately exacerbating Our study elucidates epigenetic promotes diabetes.Funding: This work supported Changzhou Municipal Health Commission (CQ20210122), Project Medical Center Nanjing University (CZKYCMCB202209), China Postdoctoral Science Foundation (2023M730372).Declaration Interest: All authors declared they have no conflict interest.Ethical Approval: vivo experiments were approved Animal Care Research Committee (China). animal procedures performed accordance with Guidelines Experiments from Ethics, National Department (1998).

Language: Английский

Lactate-induced lactylation and cardiometabolic diseases: From epigenetic regulation to therapeutics DOI

Jie Lin,

Jun Ren

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(6), P. 167247 - 167247

Published: May 16, 2024

Language: Английский

Citations

9
A new mechanism of arterial calcification in diabetes: interaction between H3K18 lactylation and CHI3L1 DOI Creative Commons
Yi Zhun Zhu,

Jingchen Chen,

Jiali Zhang

et al.

Clinical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation lactate the microenvironment can promote VSMC calcification diabetes, although specific mechanism remains to be fully elucidated. In this study, we explored characteristics lactylation diabetic arterial and underlying molecular mechanism. We found that high-glucose calcified VSMC, overall level was significantly increased. Mass spectrometry analysis revealed significant upregulation H3 histone lactylation. After site-specific point-mutation at K18 simulate delactylation modification, reduced. Through a combination H3K18la ChIP-seq, RNA-seq, ChIP-qPCR experiments, confirmed upregulate CHI3L1. CHI3L1 knockout alleviated osteogenic phenotype transformation mouse calcification. RNA-seq downstream signaling showed activates IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition IL-13Ra2 reduced conclude environment, site undergoes modification VSMCs, upregulating CHI3L1, which turn regulates pathway, ultimately exacerbating Our study elucidates epigenetic by promotes

Language: Английский

Citations

1
Age-associated microglial transcriptome leads to diminished immunogenicity and dysregulation of MCT4 and P2RY12/P2RY13 related functions DOI Creative Commons
Martin Škandík, Lara Frieß, Guillermo Vázquez-Cabrera

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 19, 2025

Abstract The aging process is marked by a time-dependent deterioration in cellular functions, particularly the immune and neural systems. Understanding phenotype acquisition of microglia, sentinel cells brain, crucial for understanding nature age-related neurological diseases. However, specific adopted microglia during remains subject debate contingent on chosen experimental model. To address these unresolved questions, we employed novel highly controlled approach utilizing long-term cultivated BV-2 exempted from additional external stimuli. Our findings revealed that aged microglial cells, comparison to their younger counterparts, acquire distinct gene expression profile, primarily characterized alterations response. Indeed, pro-inflammatory stimulated young exhibited similar transcriptomic profiles, yet response intensity stimulus was markedly muted microglia. Functional neurotoxic assays confirmed diminished neuronal death coculture with aged, activated underscoring compromised Furthermore, subsequent comparative analysis established datasets mice humans identified 13 overlapping genes, laying foundation identifying core signature. Particularly noteworthy were SLC16A3 P2RY13 , which consistently upregulation downregulation, respectively, across all datasets. Additionally, four other genes— CAPG LGALS3BP NRIP1 P2RY12 —were found share regulatory patterns both extrinsic activation. An in-depth investigation focused encoding high-affinity lactate transporter MCT4, disruptions extracellular acidification rate concentration age. Microglial purine sensing motility capacities, regulated P2RY12/P2RY13, displayed alterations. Remarkably, protein human brain tissue validated observed MCT4 downregulation In conclusion, our study unveils responsiveness. Through integration vitro cultured primary datasets, identify critical molecular determinants human-aged tissue. This comprehensive offers potential insights potentially reprogramming implications combating disorders.

Language: Английский

Citations

1
Lactylation: The Metabolic Accomplice Shaping Cancer's Response to Radiotherapy and Immunotherapy DOI
Danqing Yu, Qingping Zhong, Yanlin Wang

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102670 - 102670

Published: Jan. 1, 2025

Language: Английский

Citations

1
The Role of Lactate Metabolism in Heart Failure and Cardiogenic Shock: Clinical Insights and Therapeutic Implications. DOI
Melana Yuzefpolskaya, Sarah M. Schwartz, Annamaria Ladanyi

et al.

Journal of Cardiac Failure, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Insight into the roles of lactylation in macrophages: functions and clinical implications DOI

Min Shu,

Dingci Lu,

Ziyi Zhu

et al.

Clinical Science, Journal Year: 2025, Volume and Issue: 139(02), P. 151 - 169

Published: Jan. 1, 2025

Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, recognizing lactyl groups on proteins. Macrophages, cells of the immune system, maintain homeostasis, responding dynamically diverse internal external stimuli. Emerging researches unveil that lactylation, inducing macrophage activation polarization, affects functionality pathological conditions such inflammation, tumor microenvironment, fibrosis. Evidence progressively indicates lactate-driven alterations levels within macrophages can influence pathogenesis numerous diseases. This review aims systematically summarize research progress macrophages, explore its functions mechanisms which contributes pathology different disease phenotypes, propose future directions along with potential diagnostic therapeutic strategies.

Language: Английский

Citations

1
Lactylation in cancer: metabolic mechanism and therapeutic strategies DOI Creative Commons
Ying Sui, Ziyang Shen, Zhenling Wang

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 20, 2025

Recent progress in cancer metabolism research has identified lactylation as a critical post-translational modification influencing tumor development and progression. The process relies on lactate accumulation the activation of lactate-sensitive acyltransferases. Beyond its role epigenetic regulation, emerged significant factor evolution, offering fresh opportunities for developing targeted therapies that transcend traditional approaches. This review explores growing importance biology highlights potential advancing diagnostic tools therapeutic strategies.

Language: Английский

Citations

1
Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues DOI Creative Commons

Bangjun Xu,

Yi Liu, Ning Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 21, 2024

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

Language: Английский

Citations

7
Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications DOI Creative Commons

Chuncha Bao,

Qing Ma, Xuchao Ying

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 111, P. 105502 - 105502

Published: Dec. 10, 2024

Language: Английский

Citations

5
Lactate promotes premature aging of preeclampsia placentas through histone lactylation-regulated GADD45A DOI
Xiang Li, Qiang-Hua Wang,

J. Fei

et al.

Placenta, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0