Regulated cell death pathways in kidney disease

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(5), P. 281 - 299

Published: March 23, 2023

Language: Английский

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Oxidative stress and the role of redox signalling in chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 20(2), P. 101 - 119

Published: Oct. 19, 2023

Language: Английский

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The Road from AKI to CKD: Molecular Mechanisms and Therapeutic Targets of Ferroptosis

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 13, 2023

Abstract Acute kidney injury (AKI) is a prevalent pathological condition that characterized by precipitous decline in renal function. In recent years, growing body of studies have demonstrated maladaptation following AKI results chronic disease (CKD). Therefore, targeting the transition to CKD displays excellent therapeutic potential. However, mechanism mediated multifactor, and there still lack effective treatments. Ferroptosis, novel nonapoptotic form cell death, believed role progression. this study, we retrospectively examined history characteristics ferroptosis, summarized ferroptosis’s research progress CKD, discussed how ferroptosis participates regulating progression CKD. Furthermore, highlighted limitations present projected future evolution ferroptosis. We hope work will provide clues for further contribute study targets prevent diseases.

Language: Английский

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Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Feb. 7, 2023

Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury death, leading acute kidney the transformation of chronic disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown promote injury. this preclinical study, we investigate role mechanism exosomes (HucMSC-Exos) on repair renal after injury.C57BL/6 mice underwent unilateral ureteral obstruction, was induced in HK-2 by cisplatin. HucMSC-Exos were assessed vivo vitro. The extent injury, activation necroptosis pathway, mitochondrial quality-control-related factors determined different groups. We also analyzed possible regulatory effector molecules transcriptomics.HucMSC-Exo inhibited promoted dephosphorylation S637 site Drp1 gene reducing expression PGAM5. This subsequently fission maintained functional homeostasis, mitigating promoting repair. addition, HucMSC-Exo displayed a targeting RIPK1 through miR-874-3p.The collective findings present study demonstrate that regulate miR-874-3p attenuate enhance repair, providing new therapeutic modalities ideas for AKI process CKD mitigate damage.

Language: Английский

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Ferroptosis in Cancer: Mechanisms, Therapeutic Strategies, and Clinical Implications

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155907 - 155907

Published: March 12, 2025

Language: Английский

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Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells

Journal of Leukocyte Biology, Journal Year: 2022, Volume and Issue: 112(5), P. 1065 - 1077

Published: June 30, 2022

Acute kidney injury (AKI) represents a prevailing complication of sepsis, and its onset involves ferroptosis. Ginsenoside Rg1 exerts positive effect on diseases. This study explored the action ginsenoside in sepsis-induced AKI (SI-AKI) by regulating ferroptosis renal tubular epithelial cells (TECs). Sepsis rat models were established using cecal ligation puncture (CLP) cell treating human TECs (HK-2) with LPS to induce Serum creatinine (SCr) blood urea nitrogen (BUN) urine KIM1 contents rats determined ELISA kits. Kidney tissues subjected immunohistochemical H&E stainings. Iron concentration, malondialdehyde (MDA), glutathione (GSH), ferroptosis-related protein (ferritin light chain [FTL], ferritin heavy [FTH], GSH peroxidase 4 [GPX4], Ferroptosis suppressor 1 [FSP1]) levels HK-2 measured kits Western blotting. viability was detected counting kit-8, death observed via propidium iodide staining. Reactive oxygen species accumulation C11 BODIPY 581/591 as molecular probe. In CLP rats, reduced SCr, BUN, KIM1, NGAL levels, thus palliating SI-AKI. Additionally, decreased iron content, FTL, FTH, MDA elevated GPX4, FSP1, thereby inhibiting lipid peroxidation Moreover, FSP1 knockdown annulled inhibition vitro experiments, raised lowered during ferroptosis, antiferroptosis activity dependent FSP1. alleviates SI-AKI, possibly resulting from through

Language: Английский

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GSDMD-dependent neutrophil extracellular traps promote macrophage-to-myofibroblast transition and renal fibrosis in obstructive nephropathy

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(8)

Published: Aug. 8, 2022

Renal fibrosis is a common consequence of various progressive nephropathies, including obstructive nephropathy, and ultimately leads to kidney failure. Infiltration inflammatory cells prominent feature renal injury after draining blockages from the kidney, correlates closely with development fibrosis. However, underlying molecular mechanism behind promotion by remains unclear. Herein, we showed that unilateral ureteral obstruction (UUO) induced Gasdermin D (GSDMD) activation in neutrophils, abundant neutrophil extracellular traps (NETs) formation macrophage-to-myofibroblast transition (MMT) characterized α-smooth muscle actin (α-SMA) expression macrophages. Gsdmd deletion significantly reduced infiltration kidneys inhibited NETs formation, MMT thereby Chimera studies confirmed bone marrow-derived cells, instead parenchymal provided protection against Further, specific neutrophils macrophages protected undergoing UUO. Single-cell RNA sequencing identified robust crosstalk between In vitro, GSDMD-dependent triggered p65 translocation nucleus, which boosted production cytokines α-SMA activating TGF-β1/Smad pathway. addition, demonstrated caspase-11, could cleave GSDMD, was required for Collectively, our findings demonstrate caspase-11/GSDMD-dependent promote facilitating inflammation MMT, therefore highlighting role mechanisms

Language: Английский

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Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(7), P. 1356 - 1356

Published: July 12, 2022

Acute kidney injury (AKI) and chronic disease (CKD) are interconnected conditions, CKD is projected to become the fifth leading global cause of death by 2040. New therapeutic approaches needed. Mitochondrial dysfunction oxidative stress have emerged as drivers in acute settings, promoting AKI-to-CKD transition. In this work, we review role mitochondrial AKI progression discuss novel approaches. Specifically, evidence for diverse models (nephrotoxicity, cytokine storm, ischemia-reperfusion injury) (diabetic disease, glomerulopathies) discussed; clinical implications information on key mitochondria-related transcriptional regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha, transcription factor EB (PGC-1α, TFEB), carnitine palmitoyl-transferase 1A (CPT1A) addressed; current status development targeting mitochondria updated; barriers mitochondria-targeted interventions discussed, including lack diagnostic tests that allow us categorize baseline renal dysfunction/mitochondrial monitor its response intervention. Finally, milestones further research proposed.

Language: Английский

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Programmed Cell Death in Sepsis Associated Acute Kidney Injury

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: May 17, 2022

Sepsis-associated acute kidney injury (SA-AKI) is common in patients with severe sepsis, and has a high incidence rate mortality ICU patients. Most progress to AKI before drug treatment initiated. Early studies suggest that the main mechanism of SA-AKI sepsis leads vasodilation, hypotension shock, resulting insufficient renal blood perfusion, finally leading tubular cell ischemia necrosis. Research results recent years have shown programmed death such as apoptosis, necroptosis, pyroptosis autophagy play important roles. In early stage sepsis-related AKI, bodies form inhibit various types death. With disease, begins. Apoptosis promoter represents caspase-8-induced apoptosis effector caspase-3-induced however, caspase-11 caspase-1 regulate gasdermin D-mediated pyroptosis. Caspase-8 receptor interacting kinase 1 mediate necroptosis. This review focuses on pathophysiological mechanisms AKI.

Language: Английский

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Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair

Cell Reports, Journal Year: 2022, Volume and Issue: 41(6), P. 111610 - 111610

Published: Nov. 1, 2022

In both humans and mice, repair of acute kidney injury is worse in males than females. Here, we provide evidence that this sexual dimorphism results from sex differences ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. Using genetic single-cell transcriptomic approaches report female confers striking protection against which was experimentally induced proximal tubular (PT) cells by deleting glutathione peroxidase 4 (Gpx4). Single-cell analyses further identify the NFE2-related factor 2 (NRF2) antioxidant protective pathway as a resilience mechanism ferroptosis. Genetic inhibition pharmacological activation studies show NRF2 controls PT fate plasticity regulating Importantly, protects male ferroptosis improves cellular Our data highlight potential therapeutic target to prevent failed renal after sexes modulating plasticity.

Language: Английский

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