Oxidative Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne’s Thread

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(15), P. 3711 - 3711

Published: July 29, 2019

Amplification of oxidative stress is present since the early stages chronic kidney disease (CKD), holding a key position in pathogenesis renal failure. Induction pro-oxidant enzymes with excess generation reactive oxygen species (ROS) and accumulation dityrosine-containing protein products produced during (advanced oxidation products-AOPPs) have been directly linked to podocyte damage, proteinuria, development focal segmental glomerulosclerosis (FSGS) as well tubulointerstitial fibrosis. Vascular considered play critical role CKD progression, ROS are potential mediators impaired myogenic responses afferent arterioles autoregulation. Both inflammation hallmarks. Oxidative promotes via formation proinflammatory oxidized lipids or AOPPs, whereas activation nuclear factor κB transcription milieu expression cytokines recruitment cells. Accumulating evidence implicates various clinical models CKD, including diabetic nephropathy, IgA polycystic cardiorenal syndrome. The scope this review tackle issue holistic manner so provide future framework for interventions.

Language: Английский

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Berberine Protects Glomerular Podocytes via Inhibiting Drp1-Mediated Mitochondrial Fission and Dysfunction

Theranostics, Journal Year: 2019, Volume and Issue: 9(6), P. 1698 - 1713

Published: Jan. 1, 2019

Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis diabetic kidney disease (DKD).However, mechanisms by which FFA leads to damage glomerular podocytes DKD effects Berberine (BBR) on are not fully understood.Methods: Using db/db mice model cultured mouse podocytes, we investigated molecular mechanism FFA-induced disturbance testified BBR regulating dysfunction, podocyte apoptosis glomerulopathy progression DKD.Results: Intragastric administration for 8 weeks significantly reversed glucose lipid metabolism disorders, damage, basement membrane thickening, mesangial expansion glomerulosclerosis.BBR strongly inhibited apoptosis, increased reactive oxygen species (ROS) generation, fragmentation dysfunction both vivo vitro.Mechanistically, could stabilize morphology via abolishing palmitic (PA)-induced activation dynamin-related protein 1 (Drp1).Conclusions: Our study demonstrated first time that may have a previously unrecognized role protecting glomerulus positively Drp1-mediated dynamics.It might serve as novel therapeutic drug treatment DKD.

Language: Английский

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Autophagy in Chronic Kidney Diseases

Cells, Journal Year: 2019, Volume and Issue: 8(1), P. 61 - 61

Published: Jan. 16, 2019

Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles proteins. Current evidence suggests that autophagy critical in kidney physiology homeostasis. In clinical studies, activations inhibitions are linked to acute injuries, chronic diseases, diabetic nephropathies, polycystic diseases. Oxidative stress, inflammation, mitochondrial dysfunction, which implicated as important mechanisms underlying many modulate the activation inhibition lead dysfunction. Abnormal function can induce loss podocytes, damage proximal tubular cells, glomerulosclerosis. After activated protects cells from apoptosis enhances regeneration. Patients with diseases have impaired cannot be reversed by hemodialysis. Multiple nephrotoxic medications also alter signaling, mechanistic insights drugs revealed, thus providing unique opportunity manage nephrotoxicity these drugs. this review, we summarize current concepts its molecular aspects different pathophysiology. We discuss injury, disease, toxic effects drugs, aging kidneys. addition, examine therapeutic possibilities targeting system

Language: Английский

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METTL3-mediated m6A modification of TIMP2 mRNA promotes podocyte injury in diabetic nephropathy

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(4), P. 1721 - 1740

Published: Jan. 4, 2022

Epigenetic changes are present in many physiological and pathological processes. The N6-methyladenosine (m6A) modification is the most common eukaryotic mRNA. However, role of m6A diabetic nephropathy (DN) remains elusive. Here, we found that was significantly upregulated kidney type 1 2 mice, which caused by elevated levels METTL3. Moreover, METTL3 increased podocyte renal biopsy from patients with DN, related to damage. knockout reduced inflammation apoptosis high glucose (HG)-stimulated podocytes, while its overexpression aggravated these responses vitro. Podocyte-conditional alleviated injury albuminuria streptozotocin (STZ)-induced mice. Therapeutically, silencing adeno-associated virus serotype-9 (AAV9)-shMETTL3 vivo mitigated histopathological STZ-induced mice db/db Mechanistically, modulated Notch signaling via TIMP2 an insulin-like growth factor mRNA binding protein (IGF2BP2)-dependent manner exerted pro-inflammatory pro-apoptotic effects. In summary, this study suggested METTL3-mediated important mechanism DN. Targeting through writer enzyme a potential approach for treatment

Language: Английский

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Up-Date on Diabetic Nephropathy

Life, Journal Year: 2022, Volume and Issue: 12(8), P. 1202 - 1202

Published: Aug. 8, 2022

Diabetes is one of the leading causes kidney disease. Diabetic disease (DKD) a major cause end-stage (ESKD) worldwide, and it linked to an increase in cardiovascular (CV) risk. nephropathy (DN) increases morbidity mortality among people living with diabetes. Risk factors for DN are chronic hyperglycemia high blood pressure; renin-angiotensin-aldosterone system blockade improves glomerular function CV risk these patients. Recently, new antidiabetic drugs, including sodium-glucose transport protein 2 inhibitors glucagon-like peptide-1 agonists, have demonstrated additional contribution delaying progression enhancing outcomes. The therapeutic goal regression albuminuria, but atypical form non-proteinuric diabetic (NP-DN) also described. In this review, we provide state-of-the-art evaluation current treatment strategies promising emerging treatments.

Language: Английский

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Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115670 - 115670

Published: Oct. 13, 2023

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, posing significant challenges in terms early prevention, clinical diagnosis, and treatment. Consequently, it has emerged as major contributor to end-stage renal disease. The glomerular filtration barrier, composed podocytes, endothelial cells, the basement membrane, plays vital role maintaining function. Disruptions podocyte function, including hypertrophy, shedding, reduced density, apoptosis, can impair integrity resulting elevated proteinuria, abnormal rate, increased creatinine levels. Hence, recent research increasingly focused on injury DN, with growing emphasis exploring therapeutic interventions targeting injury. Studies have revealed that factors such lipotoxicity, hemodynamic abnormalities, oxidative stress, mitochondrial dysfunction, impaired autophagy contribute This review aims summarize underlying mechanisms DN provide an overview current status regarding experimental drugs DN. findings presented herein may offer potential targets strategies for management associated

Language: Английский

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High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Cigarette smoking is a well-established risk factor for renal dysfunction. Smoking associated with damage bears distinct physiological correlations in conditions such as diabetic nephropathy and obesity-induced glomerulopathy. However, the cellular molecular basis of an association remains poorly understood. High mobility group box 1(HMGB1) highly conserved non-histone chromatin protein that largely contributes to pathogenesis chronic inflammatory autoimmune diseases sepsis, atherosclerosis, kidney diseases. Hence, present study tested whether HMGB1 nicotine-induced podocyte injury. Biochemical analysis showed nicotine treatment significantly increased expression release compared vehicle treated podocytes. prior glycyrrhizin (Gly), binder, abolished Furthermore, immunofluorescent decreased functional proteins- podocin nephrin control cells. Gly attenuated reduction. In addition, desmin cell permeability permeability. Mechanistic elucidation revealed augmented toll like receptor 4 (TLR4) pre-treatment induced TLR4 upregulation. Pharmacological inhibition Resatorvid, specific inhibitor, also damage. one important mediators injury through activation.

Language: Английский

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Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy

Antioxidants, Journal Year: 2020, Volume and Issue: 9(10), P. 925 - 925

Published: Sept. 27, 2020

Diabetes prevalence is increasing worldwide, especially through the increase of type 2 diabetes. Diabetic nephropathy occurs in up to 40% diabetic patients and leading cause end-stage renal disease. Various factors affect development progression nephropathy. Hyperglycaemia increases free radical production, resulting oxidative stress, which plays an important role pathogenesis Free radicals have a short half-life are difficult measure. In contrast, oxidation products, including lipid peroxidation, protein oxidation, nucleic acid longer lifetimes used evaluate stress. recent years, different stress biomarkers associated with been found. This review summarises current evidence Although some them promising, they cannot replace currently clinical (eGFR, proteinuria)

Language: Английский

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Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy

Antioxidants and Redox Signaling, Journal Year: 2018, Volume and Issue: 29(4), P. 355 - 376

Published: Jan. 16, 2018

Altered activities of long noncoding RNAs (lncRNAs) have been implicated in the regulation microRNAs. microRNA-27a (miR-27a) upregulation has shown to induce endoplasmic reticulum (ER) stress podocyte injury diabetic nephropathy (DN). Herein, we aim interrogate mutually regulated network miR-27a with intergenic RNA 1619 (LINC01619) and target gene.LINC01619 downregulation was found human DN renal biopsy tissues contributed proteinuria diminished function. LINC01619 expressed cytoplasm involved ER signaling pathway. exerted biological function by serving as a "sponge" for miR-27a, which negatively targeted forkhead box protein O1 (FOXO1) activated stress. In rats high-glucose cultured podocytes, triggered oxidative injuries demonstrated increased apoptosis, diffuse foot process effacement, decreased Innovation Conclusion: This study demonstrates that functions competing endogenous regulates miR-27a/FOXO1-mediated DN. Antioxid. Redox Signal. 29, 355-376.

Language: Английский

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MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy

Cell Death and Disease, Journal Year: 2017, Volume and Issue: 8(3), P. e2658 - e2658

Published: March 9, 2017

Abstract Podocyte injury has a pivotal role in the pathogenesis of diabetic nephropathy (DN). MicroRNA-27a (miR-27a), peroxisome proliferator-activated receptor γ (PPAR ) and β -catenin pathways have been involved DN. Herein, we asked whether miR-27a mediates podocyte through PPAR γ/β signaling The functional relevance miR-27a, were investigated cultured podocytes glomeruli rats patients using vitro vivo approaches. was assessed by migration, invasion apoptosis assay. Biological parameters analyzed enzyme-linked immunosorbent We found that high glucose stimulated expression, which, negatively targeting , activated as evidenced upregulation target genes, snail1 α -smooth muscle actin ( -SMA) downregulation podocyte-specific markers podocin synaptopodin. These changes caused demonstrated increased mesenchymal transition, disrupted architectural integrity apoptosis. Furthermore, provide evidence contributed to unfavorable renal function rats. Notably, exhibited clinical biological it linked elevated serum creatinine, proteinuria reduced creatinine clearance rate. In addition, activation verified biopsy samples from DN patients. propose novel miR-27a/PPAR axis fostering progression toward more deteriorated Targeting could be potential therapeutic approach for

Language: Английский

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