T cell metabolism in kidney immune homeostasis DOI Creative Commons
Zhirong Liu,

Binbin Dai,

Jiwen Bao

et al.

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

Published: Dec. 16, 2024

Kidney immune homeostasis is intricately linked to T cells. Inappropriate differentiation, activation, and effector functions of cells lead a spectrum kidney disease. While executing functions, undergo series metabolic rewiring meet the rapid energy demand. The key enzymes metabolites involved in cell metabolism metabolically epigenetically modulate cells' thereby being capable modulating homeostasis. In this review, we first summarize latest advancements immunometabolism. Second, outline alterations renal microenvironment under certain disease conditions. Ultimately, highlight modulation within homeostasis, which may shed light on new strategies for treating

Language: Английский

Exploring the diverse role of pyruvate kinase M2 in cancer: Navigating beyond glycolysis and the Warburg effect DOI

Saurabh Upadhyay,

Shumayila Khan, Md. Imtaiyaz Hassan

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(3), P. 189089 - 189089

Published: March 6, 2024

Language: Английский

Citations

19
Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease DOI Creative Commons
Yulan Chen, Xueyuan Bai, Jianwen Chen

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 57(2)

Published: Sept. 25, 2023

Abstract We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in progression acute kidney injury (AKI) chronic disease (CKD). The PKM2 pericyte‐myofibroblast transdifferentiation was investigated an AKI‐CKD mouse model. Platelet growth factor receptor beta (PDGFRβ)‐iCreERT2; tdTomato mice were used for tracing. Western blotting and immunofluorescence staining examine protein expression. An 5‐ethynyl‐2′‐deoxyuridine assay measure proliferation. A scratch cell migration analyse migration. Seahorse experiments glycolytic rates. Enzyme‐linked immunoassay enzymatic activity lactate concentrations. nuclear translocation inhibitors Shikonin TEPP‐46 alter transdifferentiation. In AKI‐CKD, pericytes proliferated transdifferentiated into myofibroblasts is highly expressed pericytes. inhibited proliferation, migration, by reducing entry. nucleus, promoted downstream dehydrogenase (LDHA) glucose transporter 1 (GLUT1) transcription, which are critical glycolysis. Therefore, regulates production, PKM2‐regulated regulating LDHA GLUT1 transcription production. Reducing import can reduce pericytes‐myofibroblasts transdifferentiation, providing new ideas treatment.

Language: Английский

Citations

18
CircRNA-0013747 Promotes Mesangial Cell Proliferation in Immunoglobulin A Nephropathy through Modulation of the Warburg Effect DOI Creative Commons
Huimei Zou,

Wenli Deng,

Lifen Xu

et al.

Journal of physiological investigation., Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Immunoglobulin A nephropathy (IgAN) is characterized by aberrant mesangial cell (MC) proliferation, which a critical determinant of glomerular sclerosis and renal dysfunction. Previous studies have highlighted the role pyruvate kinase M2 (PKM2)- mediated aerobic glycolysis in promoting MC growth progression kidney diseases. However, precise mechanisms underlying PKM2 dysregulation IgAN remain unclear. Circular RNAs (circRNAs), class noncoding RNAs, emerged as pivotal regulators various diseases, yet their has not been fully elucidated. In this study, we investigated expression functional significance circRNA_0013747 IgAN, focusing on its interaction with microRNA-330-3p (miR-330-3p) downstream effects PKM2-mediated glycolysis. Our results demonstrated significant upregulation biopsy samples from patients. Functional analyses revealed that promoted proliferation activated Importantly, these were attenuated miR-330-3p, was found to physically interact circRNA_0013747, thereby inhibiting function. Mechanistically, acted sponge for relieving suppressive expression. These findings suggest enhances MCs through modulation miR-330-3p/PKM2 signaling axis. offer novel insights into pathogenesis could contribute new therapeutic approaches disease. Specifically, targeting or modulating miR-330-3p may provide means inhibit glycolysis, slowing preserving Such strategies hold promise substantial benefits patients pave path toward developing more potent treatments wider range

Language: Английский

Citations

0
Ankrd1 as a potential biomarker for the transition from acute kidney injury to chronic kidney disease DOI Creative Commons

Hailin Li,

Lemei Hu,

Changqing Zheng

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 7, 2025

Ischemia-reperfusion injury (IRI) is one of the leading causes acute kidney (AKI), predisposing patients to chronic disease (CKD) due maladaptive renal repair. Nevertheless, molecular mechanisms and biomarkers that cause repair remain unclear. In this study, we used single-nucleus RNA sequencing data from GEO database (GSE139107) identify markers during transition AKI CKD caused by IRI. Analysis intercellular crosstalk, trajectory machine learning algorithms revealed hub cell clusters genes. Proximal tubule (PT) cells, especially a new cluster (New PT2), significantly interacted with fibroblasts transition. The expression levels genes were validated using bulk RNA-seq (GSE98622) further confirmed through RT-qPCR immunohistochemical analysis in ischemia-reperfusion (uIRI) mice. Ankrd1, gene New PT2, showed sustained upregulation proximal AKI. Compared sham-operated group, Ankrd1 mice increased at 0.5 days post-reperfusion, peaked day 1, remained elevated up 60 days. This study indicated was positively associated progression may potentially serve as valuable biomarker for transitional process.

Language: Английский

Citations

0
Macrophage polarization-mediated PKM2/mTORC1/YME1L signaling pathway activation in fibrosis associated with Cardiorenal syndrome DOI
Xuefeng Zhang, Wenyu Shao,

Yun Gao

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111664 - 111664

Published: Feb. 1, 2025

Language: Английский

Citations

0
Metabolite pathway alterations identified by magnetic resonance metabolomics in a proximal tubular epithelial cell line treated with TGF‐β1 DOI Creative Commons
Tyrone L. R. Humphries, Soobin Lee,

Aaron Urquhart

et al.

Physiological Reports, Journal Year: 2025, Volume and Issue: 13(4)

Published: Feb. 1, 2025

Abstract Tubulointerstitial fibrosis is a characteristic hallmark of chronic kidney disease (CKD). Metabolic perturbations in cellular energy metabolism contribute to the pathogenesis CKD, but chemical contributors remain unclear. The aim this investigation was use two dimensional 1 H‐nuclear magnetic resonance (2D‐COSY) metabolomics identify changes fibrogenesis. An vitro transforming growth factor‐β1 (TGF‐β1)‐induced model fibrogenesis with human kidney‐2 (HK‐2) proximal tubular epithelial cells (PTEC) used. validated by assaying for various pro‐fibrotic molecules, using quantitative PCR and Western blotting. 2D‐COSY performed on treated cells. Morphological functional tubulointerstitial were confirmed model; expression fibronectin, collagen type IV, smooth muscle actin, oxidative stress enzymes increased ( p < 0.05). NMR provided evidence altered metabolite signatures associated glycolysis glutamine metabolism, decreased myo‐inositol choline, metabolites phase pentose phosphate pathway glucose glucuronic acid. PTEC likely supports rapid fibrogenic demands. These results, metabolomics, support development biomarker panel detectable clinical spectroscopy diagnose manage CKD.

Language: Английский

Citations

0
Pyruvate kinase M2 modulates mitochondrial dynamics and EMT in alveolar epithelial cells during sepsis-associated pulmonary fibrosis DOI Creative Commons

Jinhua Feng,

Xi Huang, Yawen Peng

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 19, 2025

Language: Английский

Citations

0
Lactate and Lactylation in AKI‐to‐CKD: Epigenetic Regulation and Therapeutic Opportunities DOI Creative Commons

Yi Hou,

Dongwei Liu,

Zuishuang Guo

et al.

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

ABSTRACT Lactate is not only a byproduct of glycolysis, but also considered an energy source, gluconeogenic precursor, signalling molecule and protein modifier during the process cellular metabolism. The discovery lactylation reveals multifaceted functions lactate in metabolism opens new avenues for lactate‐related research. Both have been implicated regulating numerous biological processes, including tumour progression, ischemic–hypoxic injury, neurodevelopment immune‐related inflammation. kidney plays crucial role metabolism, influencing levels while being regulated by lactate. Previous studies demonstrated importance pathogenesis acute injury (AKI) chronic disease (CKD). This review explores these diseases, comparing function metabolic mechanisms normal diseased kidneys from perspective lactylation. key regulatory roles different organs, multiple systems, various pathological states underlying AKI‐to‐CKD progression are summarised. Moreover, potential therapeutic targets future research directions across diseases identified.

Language: Английский

Citations

0
Novel molecular mechanisms of immune evasion in hepatocellular carcinoma: NSUN2‐mediated increase of SOAT2 RNA methylation DOI Creative Commons
Jinhua Jiang, Feng Liu, Dan Cui

et al.

Cancer Communications, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract Background Hepatocellular carcinoma (HCC) is a deadly malignancy known for its ability to evade immune surveillance. NOP2/Sun RNA methyltransferase family member 2 (NSUN2), an involved in carcinogenesis, has been associated with evasion and energy metabolism reprogramming. This study aimed examine the molecular mechanisms underlying involvement of NSUN2 metabolic reprogramming HCC. Methods Single‐cell transcriptomic sequencing was applied cellular composition changes, particularly cell dynamics, HCC adjacent normal tissues. Bulk RNA‐seq proteomics identified key genes proteins. Methylation methylated immunoprecipitation (MeRIP) were carried out characterize role 5‐methylcytosine (m5C) modification sterol O‐acyltransferase ( SOAT2 ). Clinical samples from 30 patients analyzed using reverse transcription‐quantitative polymerase chain reaction Western blotting. Gene expression manipulated CRISPR/Cas9 lentiviral vectors. In vitro co‐culture models metabolomics used cell‐T interactions, metabolism, evasion. Tumor growth orthotopic mouse model monitored by bioluminescence imaging, subsequent measurements tumor weight, volume, immunohistochemical staining. Results analysis marked increase malignant cells Cell communication indicated that might promote cancer progression evading clearance. Multi‐omics analyses as regulator development. MeRIP confirmed facilitated m5C . Analysis human tissue demonstrated pronounced upregulation , along elevated levels experiments uncovered augmented repressed activity cytotoxicity CD8 + T cells, contributing vivo studies further substantiated fostering formation modulating Conclusions The findings highlight critical driving through regulation on These present potential markers diagnosis therapeutic targets treatment.

Language: Английский

Citations

0
Lactylation as a metabolic epigenetic modification: Mechanistic insights and regulatory pathways from cells to organs and diseases DOI
Cong Chen, Jie Wang, Xueying Zhu

et al.

Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 156289 - 156289

Published: May 1, 2025

Language: Английский

Citations

0