Targeting the progression of chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 16(5), P. 269 - 288

Published: Feb. 14, 2020

Language: Английский

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Kidney fibrosis: from mechanisms to therapeutic medicines

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 17, 2023

Abstract Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading scarring, a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. fibrosis identified tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, vascular rarefaction. Fibrotic niche, where organ initiates, complex interplay between injured parenchyma (like tubular cells) multiple non-parenchymal cell lineages (immune mesenchymal located spatially within scarring areas. Although the mechanisms are complicated due kinds cells involved, with help single-cell technology, many key questions have been explored, such as what kind renal tubules profibrotic, myofibroblasts originate, which immune how communicate each other. In addition, genetics epigenetics deeper that regulate fibrosis. And reversible nature epigenetic changes including DNA methylation, RNA interference, chromatin remodeling, gives an opportunity stop or reverse therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) developed delay progression recent years. Furthermore, better understanding also favored discover biomarkers fibrotic injury. review, we update advances mechanism summarize novel treatment for CKD.

Language: Английский

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Signaling pathways of chronic kidney diseases, implications for therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 9, 2022

Abstract Chronic kidney disease (CKD) is a chronic renal dysfunction syndrome that characterized by nephron loss, inflammation, myofibroblasts activation, and extracellular matrix (ECM) deposition. Lipotoxicity oxidative stress are the driving force for loss of including tubules, glomerulus, endothelium. NLRP3 inflammasome signaling, MAPK PI3K/Akt RAAS signaling involves in lipotoxicity. The upregulated Nox expression decreased Nrf2 result directly. injured resident cells release proinflammatory cytokines chemokines to recruit immune such as macrophages from bone marrow. NF-κB JAK-STAT Toll-like receptor cGAS-STING major pathways mediate inflammation inflammatory cells. produce secret great number profibrotic TGF-β1, Wnt ligands, angiotensin II. TGF-β Notch evoke activation promote generation ECM. potential therapies targeted these also introduced here. In this review, we update key lipotoxicity, stress, kidneys with injury, drugs based on latest studies. Unifying will be instrumental advance further basic clinical investigation CKD.

Language: Английский

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Role of miRNA and lncRNAs in organ fibrosis and aging

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 143, P. 112132 - 112132

Published: Sept. 1, 2021

Fibrosis is the endpoint of pathological remodeling. This process contributes to pathogenesis several chronic disorders and aging-associated organ damage. Different molecular cascades contribute this process. TGF-β, WNT, YAP/TAZ signaling pathways have prominent roles in A number long non-coding RNAs microRNAs been found regulate fibrosis through modulation activity related pathways. miR-144-3p, miR-451, miR-200b, miR-328 are among that participate pathology cardiac fibrosis. Meanwhile, miR-34a, miR-17-5p, miR-122, miR-146a, miR-350 liver different situations. PVT1, MALAT1, GAS5, NRON, PFL, MIAT, HULC, ANRIL, H19 We review impact aging-related pathologies.

Language: Английский

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Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(8), P. 528 - 542

Published: May 10, 2021

Language: Английский

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Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Language: Английский

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Loss of endothelial glucocorticoid receptor accelerates diabetic nephropathy

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 22, 2021

Language: Английский

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The Link Between the Mitochondrial Fatty Acid Oxidation Derangement and Kidney Injury

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: July 9, 2020

Renal proximal tubular cells are high energy-demanding mainly relying on fatty acid oxidation. In stress conditions, such as transient hypoxia, oxidation (FAO) decreases and carbohydrate catabolism fails to compensate for the energy demand. this scenario, surviving exhibit peculiar phenotype associating with fibrosis that is histological manifestation of a process culminating in chronic end-stage kidney disease. Genome-wide transcriptome analysis revealed that, together inflammation, FAO top dysregulated pathway diseases lowered expression key enzymes regulators. Another evidence links derangement progressive decrease peroxisome proliferator-activated receptor α (PPARα), master regulator enzymes, aged people triggers age-associated renal fibrosis. To allow FAO, coordinate network transport proteins required. Indeed, mitochondrial inner membrane impermeable acyl-CoAs specialized system, well known carnitine shuttle, needed translocate acids moieties, conjugated carnitine, into matrix β-oxidation. The first component system palmitoyltransferase 1 (CPT1) responsible transfer acyl moieties carnitine. Several studies indicated stimulation CPT1 activity has protective effect against Therefore, transporters linked may represent potential pharmacological targets deserving further attention development new drugs attenuate dysfunction.

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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Targeting the Hypoxic and Acidic Tumor Microenvironment with pH-Sensitive Peptides

Cells, Journal Year: 2021, Volume and Issue: 10(3), P. 541 - 541

Published: March 4, 2021

The delivery of cancer therapeutics can be limited by pharmacological issues such as poor bioavailability and high toxicity to healthy tissue. pH-low insertion peptides (pHLIPs) represent a promising tool overcome these limitations. pHLIPs allow for the selective agents tumors on basis pH, taking advantage acidity hypoxic tumor microenvironment. This review article highlights various applications in which have been utilized targeting treating diseases environments, including small molecule inhibitors, toxins, nucleic acid analogs, fluorescent dyes, nanoparticles.

Language: Английский

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