Slc25a21 in cisplatin-induced acute kidney injury: a new target for renal tubular epithelial protection by regulating mitochondrial metabolic homeostasis DOI Creative Commons
Xin Su, Mi Bai,

Yaqiong Shang

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(12)

Published: Dec. 18, 2024

Abstract Acute kidney injury (AKI) is a significant global health issue, which often caused by cisplatin therapy and characterized mitochondrial dysfunction. Restoring homeostasis in tubular cells could exert therapeutic effects. Here, we investigated Slc25a21, carrier, as potential target for AKI intervention. Renal Slc25a21 expression negatively associated with function both patients cisplatin-induced murine models. Sustaining renal of slowed down progression reducing cellular apoptosis, necroptosis, the inflammatory response, likely through its regulation 2-oxoadipate conversion. highly expressed proximal epithelial cells, down-regulation contributes to compromised biogenesis integrity, well impaired oxidative phosphorylation. Mechanistically, reduced disrupts transport, affecting related metabolites influx tricarboxylic acid cycle. These findings demonstrate previously unappreciated metabolic suggest that targeting sustaining be novel strategy AKI.

Language: Английский

Renal tubular epithelial cells response to injury in acute kidney injury DOI Creative Commons
Zuo‐Lin Li, Xinyan Li, Yan Zhou

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 107, P. 105294 - 105294

Published: Aug. 23, 2024

Acute kidney injury (AKI) is a clinical syndrome characterized by rapid and significant decrease in renal function that can arise from various etiologies, associated with high morbidity mortality. The tubular epithelial cells (TECs) represent the central cell type affected AKI, their notable regenerative capacity critical for recovery of afflicted patients. adaptive repair process initiated surviving TECs following mild AKI facilitates full recovery. Conversely, when severe or persistent, it allows to undergo pathological responses, abnormal phenotypic transformation, which will lead development fibrosis. Given implications fate after outcomes, deeper understanding these mechanisms necessary identify promising therapeutic targets biomarkers human kidney.

Language: Английский

Citations

14
Identification and Functional Analysis of Energy Metabolism and Pyroptosis-Related Genes in Diabetic Nephropathy DOI Creative Commons
Shan He, Jian Ye, Yu Wang

et al.

Heliyon, Journal Year: 2025, Volume and Issue: 11(3), P. e42201 - e42201

Published: Jan. 23, 2025

Energy metabolism and pyroptosis are integral to the pathogenesis of diabetic nephropathy (DN). However, precise roles energy in DN development remain unclear. This study aims elucidate metabolism- pyroptosis-related differentially expressed genes (EMAPRDEGs) development. EMAPRDEGs were identified by querying GeneCards Gene Expression Omnibus (GEO) databases. Subsequent analyses included Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment, Set Enrichment Analysis (GSEA), Protein-Protein Interaction (PPI) network analysis. Additionally, mRNA-miRNA, mRNA-drug, mRNA-transcription factor (TF) interaction networks constructed. Differential expression receiver operating characteristic (ROC) curve performed evaluate diagnostic potential EMAPRDEGs. Immune cell infiltration was assessed using ssGSEA algorithm, levels tissues validated quantitative real-time PCR (qRT-PCR). Thirteen identified, with GO KEGG indicating their involvement pathways. GSEA revealed significant enrichment these biological pathways associated nephropathy. PPI analysis highlighted central role within relevant Predictive modeling demonstrated interactions between EMAPRDEGs, 69 miRNAs, 117 TFs. showed substantial alterations immune populations, ADH1B PC showing a correlation natural killer cells memory B cells. ROC confirmed for qRT-PCR patterns CASP1, IL-18, PDK4, FBP1, which consistent bioinformatics predictions. Bioinformatics 13 candidate among FBP1 emerge as biomarkers

Language: Английский

Citations

0
The gut–kidney axis is regulated by astragaloside IV to inhibit cyclosporine A-induced nephrotoxicity DOI Creative Commons
Cong Han, Ranran Gao, Le Zhou

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 27, 2025

Introduction Chronic nephrotoxicity caused by CNIs (CICN) manifests clinically as chronic kidney disease (CKD). Astragaloside IV (AS-IV) plays a certain role in the treatment of CKD. This study aimed to verify ameliorative effects AS-IV on CICN and further explore mechanisms underlying modulation “gut–transcriptome–metabolome coexpression network” within context “gut–kidney axis” improve CICN. Methods Five groups 40 mice were studied: normal group (N, olive oil), model (M, CsA, 30 mg kg -−1 d −1 ), low-dose (CsA + AS-IV, 10 high-dose 20 valsartan Val, ). The gut microbiota, renal transcriptome, urine metabolome separately detected construct gut–transcriptome–metabolome network. target species, genes, metabolites evaluated. Results CsA led increased proteinuria deterioration function, accompanied inflammation oxidative stress, whereas improved damage. inhibited intestinal permeability disrupted microbiota structure, increasing abundance Lactobacillus reuteri , Bifidobacterium animalis Ignatzschineria indica Blautia glucerasea. Six pathways related transcription metabolism, including citrate cycle ascorbate aldarate metabolism proximal tubule bicarbonate reclamation glycolysis/gluconeogenesis, ferroptosis, drug metabolism–cytochrome P450 identified. Seven identified 6 pathways, UDP-D-galacturonic acid, 2-phenylethanol glucuronide, dehydroascorbic isopentenyl pyrophosphate, alpha-D-glucose, 3-carboxy-1-hydroxypropylthiamine diphosphate citalopram aldehyde. genes Ugt1a2, Ugt1a9, Ugt1a5, Pck1, Slc7a11, also predicted NONMMUT144584.1, MSTRG.30357.1 ENSMUST00000174821. was highly correlated with function AS-IV. validated. intestinal-derived urinary toxins tissue apoptosis, lipid accumulation, collagen deposition, mitochondrial Conclusion through six energy driven L. alderate tube are important mechanisms.

Language: Английский

Citations

0
Selenium-Doped Carbon Dots as a Multipronged Nanoplatform to Alleviate Oxidative Stress and Ferroptosis for the Reversal of Acute Kidney Injury DOI
Man Li, Lijuan Yang,

Yibo An

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Acute kidney injury (AKI) is a life-threatening condition characterized by rapid decline in the renal function, primarily caused oxidative stress, inflammation, and ferroptosis. Herein, we present selenium-doped carbon dots (Zt-SeCDs) that integrate antioxidant activity with controlled release of Zileuton, 5-lipoxygenase (ALOX5) inhibitor, under high reactive oxygen species (ROS) conditions. This nanoplatform can efficiently deliver leveraging its inherent properties to achieve targeted prevention treatment AKI. In vitro studies have confirmed Zt-SeCDs eliminate excessive ROS, prevent ferroptotic cell death, modulate inflammatory responses reducing expression key pro-inflammatory cytokines. Additionally, regulate ferroptosis through suppression ALOX5 upregulation glutathione peroxidase 4 (GPX4) expression. The significantly improves promotes regeneration damaged tissue, alleviates processes, death. Moreover, monitoring serum indicators observing pathological changes further potential preventing Notably, activate AMPK/FoxO1 signaling pathway, enhancing endogenous defenses protect tissue from damage. promising not only holds significant promise for AKI, but also aims facilitate clinical application.

Language: Английский

Citations

0
Irisin Is a Potential Novel Biomarker and Therapeutic Target Against Kidney Diseases DOI

Xiu Huang,

Xiya Ren,

Limei Zhao

et al.

Cell Biochemistry and Function, Journal Year: 2025, Volume and Issue: 43(5)

Published: May 1, 2025

ABSTRACT Kidney diseases, characterized by renal dysfunction, are the leading causes of death worldwide. It is crucial to prevent and treat kidney diseases reduce their associated morbidity mortality. Moderate physical exercise has been recognized be advantageous for health. Irisin an exercise‐induced myokine that was identified in 2012. plays important role energy bone metabolism, oxidative stress reduction, anti‐inflammatory processes, cell inhibition, cardiovascular protection. However, relationship between irisin have not fully elucidated. This review explores as a biomarker disease diagnosis its complications, well mechanisms through which it participates various pathways, such apoptosis, autophagy, pyroptosis, ferroptosis. Furthermore, secretion levels were discussed provide basis prevention treatment avenues, therapeutic guidance developing new promising intervention strategies. Clinical Trial Registration : None.

Language: Английский

Citations

0
SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation DOI Creative Commons

Shengyu Pan,

Tianhui Yuan,

Yuqi Xia

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2279 - 2279

Published: Oct. 8, 2024

: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is vital influencer of RTC survival, and SMYD2 histone methylation transferase that has been extensively implicated various metabolic disorders. Hence, this research aimed identify whether induces energy RTCs exposed CaOx nephrolithiasis.

Language: Английский

Citations

2
Glutaminolysis is a Potential Therapeutic Target for Kidney Diseases DOI Creative Commons
Liping Ou, Yongjian Liu,

Shi-Tong Qiu

et al.

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2024, Volume and Issue: Volume 17, P. 2789 - 2807

Published: July 1, 2024

Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is most abundant free amino acid in body participates more metabolic processes than other acids. Altered glutamine metabolism a prominent feature different Glutaminolysis converts into TCA cycle metabolite, alpha-ketoglutarate, via cascade enzymatic reactions. This pathway plays pivotal roles inflammation, maladaptive repair, cell survival proliferation, redox homeostasis, immune regulation. Given crucial role glutaminolysis bioenergetics anaplerotic fluxes pathogenesis, studies on this could provide better understanding diseases, thus inspiring development potential methods for targeted therapy. Emerging evidence has shown that targeting promising therapeutic strategy ameliorating disease. In narrative review, equation including keywords related glutamine, are subjected an exhaustive search Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, summarize regulation major diseases its underlying molecular mechanisms. Furthermore, highlight strategies their clinical applications.

Language: Английский

Citations

1
Aquaporin-1 Facilitates Macrophage M1 Polarization by Enhancing Glycolysis Through the Activation of HIF1α in Lipopolysaccharide-Induced Acute Kidney Injury DOI

RuXue Diao,

Wuyang Lv,

Yuchen Wang

et al.

Inflammation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Language: Английский

Citations

1
An immunocompetent human kidney on-a-chip model to study renal inflammation and immune-mediated injury DOI Creative Commons
Linda Gijzen,

Marleen Bokkers,

Richa Hanamsagar

et al.

Biofabrication, Journal Year: 2024, Volume and Issue: 17(1), P. 015040 - 015040

Published: Dec. 16, 2024

Kidney damage and dysfunction is an emerging health issue worldwide resulting in high morbidity mortality rates. Numerous renal diseases are recognized to be driven by the immune system. Despite this recognition, development of targeted therapies has been challenging as knowledge underlying mechanism complex interactions remains insufficient. Recent advancements field offer promising avenues for exploring interplay between cells their role inflammation diseases. This study describes establishment a human immunocompetent 3D vitro co-culture model proximal tubule high-throughput microfluidic platform that can used functionality inflammatory processes. The incorporated RPTEC top compartment HUVECs bottom cultured under flow direct contact with collagen-I ECM gel formation polarized tubular structures. As component, primary monocytes different donors were added lumen endothelium. Renal was successfully induced using complement activated serum (CAS) evident epithelial morphological changes, increased expression adhesion molecules, release pro-inflammatory cytokines, reduced viability. Realtime migratory behavior showed extravasation migration towards upon exposure CAS donor-to-donor differences observed. Finally, modulatory compounds efficacious inhibition monocyte conditions model. A successful established applied disease but also drug screening due compatibility automation relatively throughput. Overall, described potential fill gap currently exists preclinically. .

Language: Английский

Citations

1
Targeting programmed cell death in diabetic kidney disease: from molecular mechanisms to pharmacotherapy DOI Creative Commons

Fengzhao Liu,

Zhenyu Yang, Jixin Li

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Dec. 20, 2024

Abstract Diabetic kidney disease (DKD), one of the most prevalent microvascular complications diabetes, arises from dysregulated glucose and lipid metabolism induced by hyperglycemia, resulting in deterioration renal cells such as podocytes tubular epithelial cells. Programmed cell death (PCD), comprising apoptosis, autophagy, ferroptosis, pyroptosis, necroptosis, represents a spectrum demise processes intricately governed genetic mechanisms vivo. Under physiological conditions, PCD facilitates turnover cellular populations serves protective mechanism to eliminate impaired or cells, thereby preserving tissue homeostasis amidst hyperglycemic stress. However, existing research predominantly elucidates individual modes death, neglecting intricate interplay mutual modulation observed among various forms PCD. In this comprehensive review, we delineate diverse regulatory governing elucidate crosstalk dynamics distinct pathways. Furthermore, review recent advancements understanding pathogenesis explore their implications DKD. Additionally, potential natural products derived primarily botanical sources therapeutic agents, highlighting multifaceted effects on modulating crosstalk, proposing novel strategies for DKD treatment.

Language: Английский

Citations

1