The potential mechanism of D-amino acids – mitochondria axis in the progression of diabetic kidney disease DOI Creative Commons
Hoang Thuy Linh, Yusuke Nakade, Takashi Wada

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and stands out as the leading cause end-stage renal worldwide. There increasing evidence that mitochondrial dysfunction, including impaired biogenesis, dynamics, oxidative stress, contributes to development progression DKD. D-amino acids (D-AAs), which are enantiomers L-AAs, have recently been detected in various living organisms acknowledged play important roles numerous physiological processes human body. Accumulating demonstrates D-AA levels blood or urine could serve useful biomarkers for reflecting function. The D-AAs implicated regulation cellular proliferation, generation reactive oxygen species (ROS), innate immunity. This article reviews current relating dysfunction proposes potential interaction contribution D-AAs-mitochondria axis DKD pathophysiology progression. insight provide novel therapeutic approaches preventing ameliorating based on this biological axis.

Language: Английский

Mitochondrial metabolic reprogramming in diabetic kidney disease DOI Creative Commons
Xiaoting Fan, Meilin Yang, Yating Lang

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 24, 2024

Abstract Diabetic kidney disease, known as a glomerular arises from metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play key role in substance metabolism via oxidative phosphorylation to generate ATP. Cells undergo reprogramming compensatory mechanism fulfill energy needs for survival and growth, attracting scholarly attention recent years. Studies indicate that mitochondrial significantly influences the pathophysiological progression of DKD. Alterations lead abnormal expression signaling molecules activation pathways, inducing stress-related cellular damage, inflammatory responses, apoptosis, autophagy irregularities, culminating fibrosis insufficiency. This review delves into impact on DKD pathogenesis, emphasizing regulation regulators downstream pathways. Therapeutic interventions targeting can potentially delay progression. The findings underscore importance focusing develop safer more effective therapeutic approaches.

Language: Английский

Citations

18
Novel Insights into Diabetic Kidney Disease DOI Open Access
Ewelina Młynarska, Dominika Buławska, Witold Czarnik

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10222 - 10222

Published: Sept. 23, 2024

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third type 1 and nearly half 2 patients. As the leading cause end-stage renal (ESRD) globally, DKD develops through complex interplay chronic hyperglycemia, oxidative stress, inflammation. Early detection crucial, with diagnosis based on persistent albuminuria reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, use nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) glucagon-like peptide-1 (GLP-1) agonists. Ongoing research explores novel therapies targeting molecular pathways non-coding RNAs. Preventive measures focus rigorous control hyperglycemia hypertension, aiming to mitigate progression. Despite therapeutic advances, remains ESRD, highlighting need for continued identify new biomarkers innovative treatments.

Language: Английский

Citations

14
Identification of key antifibrotic targets FPR1, TAS2R5, and LRP2BP of valsartan in diabetic nephropathy: A transcriptomics-driven study integrating machine learning, molecular docking, and dynamics simulations DOI

Zewen Wang,

Anlei Yuan,

Chaoqun Liu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139842 - 139842

Published: Jan. 13, 2025

Language: Английский

Citations

1
Could Cytoplasmic Lipid Droplets be Linked to Inefficient Oxidative Phosphorylation in Cancer? DOI
Thomas N. Seyfried,

Nathan L. Ta,

Tomás Duraj

et al.

Current Tissue Microenvironment Reports, Journal Year: 2024, Volume and Issue: 5(4), P. 109 - 117

Published: May 17, 2024

Language: Английский

Citations

8
Sodium–Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome DOI Creative Commons
Fernando Cortés-Camacho, Oscar René Zambrano-Vásquez, Elena Aréchaga-Ocampo

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 768 - 768

Published: June 26, 2024

Metabolic syndrome (MetS) is a multifactorial condition that significantly increases the risk of cardiovascular disease and chronic kidney (CKD). Recent studies have emphasized role lipid dysregulation in activating cellular mechanisms contribute to CKD progression context MetS. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated efficacy improving various components MetS, including obesity, dyslipidemia, insulin resistance. While SGLT2i shown cardioprotective benefits, underlying MetS remain poorly studied. Therefore, this review aims elucidate by which modulate metabolism their impact on resistance, mitochondrial dysfunction, oxidative stress, progression. We also explore potential benefits combining with other antidiabetic drugs. By examining beneficial effects, molecular targets, cytoprotective both natural synthetic SGLT2i, provides comprehensive understanding therapeutic managing MetS-induced CKD. The information presented here highlights significance addressing complex interplay between metabolic dysregulation, renal impairment, offering clinicians researchers valuable resource for developing improved treatment strategies personalized approaches patients

Language: Английский

Citations

4
Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism DOI Creative Commons
Phoom Narongkiatikhun, Ye Ji Choi,

Hailey Hampson

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: 9(12), P. 3386 - 3402

Published: Oct. 4, 2024

Language: Английский

Citations

4
Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src DOI Creative Commons

Xieyi Guo,

Liu Yang,

Xiao-Ning An

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 15, 2025

Abstract Background The treatment options to delay the progression of diabetic nephropathy (DN), a key contributor chronic kidney disease (CKD), are urgently needed. Previous studies reported that traditional Chinese medicine Panax notoginseng (PNG) exerted beneficial effects on DN. However, renoprotective Notoginsenoside R2 (NR2), an active component PNG, DN have not been investigated. This study aimed assess therapeutic potential NR2 in and explore its underlying mechanisms. Methods In vivo models were developed using db/db mice, while vitro utilized HK-2 cells exposed high glucose palmitic acid (HGPA). Online databases Cytoscape software employed predict targets NR2. expression associated proteins was measured immunohistochemistry western blot. Lipid accumulation, oxidative stress levels, mitochondrial function cell apoptosis also assessed. Small interfering RNA used experiments examine effect c-Src. Results ameliorated albuminuria, renal pathology mice. activation c-Src suppressed mice HGPA. inhibited JNK/STAT1 phosphorylation CD36 overexpression. lipid stress, dysfunction vitro. By inhibiting c-Src, HGPA experienced less deposition damage, indicating correlated with inhibition Conclusion delayed partly through suppression protective might be related reduction accumulation. Graphical

Language: Английский

Citations

0
Metformin alleviates sphingolipids dysregulation and improves obesity-related kidney disease in high fat diet rats DOI

Xing Lin,

Shanyu Wu,

Ying Shi

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2025, Volume and Issue: 392(3), P. 103388 - 103388

Published: Jan. 17, 2025

Obesity-related kidney disease (ORKD) has recently become a global health issue. Metformin is widely used in patients with type 2 diabetes concomitant obesity, but its effects on ORKD are insufficiently understood. Accumulation of lipid species including sphingolipids been reported to disrupt glomerular functions and drive progression chronic disease. The present study aimed test the hypothesis that metformin could exert beneficial ORKD, which may be associated changes renal lipidomics. Male Sprague-Dawley rats were divided into normal chow diet (ND) group or high-fat (HFD)-fed group. After 8 weeks, HFD-fed was subdivided treatment (HFD-Met) control (HFD-C) for an additional weeks. Sphingolipids phospholipids cortex measured by targeted Compared ND group, HFD-C developed histopathological features ORKD. alleviated dyslipidemia, dysfunction, proteinuria, hypertrophy, podocyte damage, fibrosis rats. Renal sphingolipid analysis showed elevations total ceramide, sphingosine, glucosylceramide, galactosylceramide levels versus Specific species, such as ceramide d18:1/22:0, glucosylceramide d18:1/20:0, d18:1/16:0, positively oxidative stress insulin resistance, reduced HFD-Met phospholipid increased phosphatidylcholine lysophosphatidylcholine (LPC) ratio saturated monounsaturated LPCs polyunsaturated significantly These results suggest alleviates dysregulation improves SIGNIFICANCE STATEMENT: To date, this first report explore findings reveal specific crucial deeper understanding underlying mechanisms obesity-related it. signature have significant implications developing therapeutic strategies

Language: Английский

Citations

0
Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy DOI Creative Commons
Ruijing Zhang,

Runze Chang,

Heng Wang

et al.

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

Published: Feb. 4, 2025

Diabetic nephropathy (DN) is one of the major causes end-stage renal disease. This study aimed to explore internal relationship between metabolic processes and autoimmune responses in patients with DN via untargeted metabolomics Olink proteomics. The serum 10 who were diagnosed healthy individuals Animal models used validate characterized genes. Correlation analysis differentially abundant metabolites expressed proteins revealed that SIRT2 might be a key hub linking energy metabolism innate immune responses. KEGG enrichment showed HIF-1 signaling pathway cell carcinoma co-enriched pathways inflammatory response. VEGFA plays vital role these two pathways. ability regulate expression has been demonstrated. In vivo experiments SIRT2, VEGFA, HIF-1α highly kidneys mice diabetic nephropathy. conclusion, our combines proteomics provide valuable insights into synergistic roles disorders DN. data suggest may target affecting processes.

Language: Английский

Citations

0
Renal Lipid Alterations From Diabetes to Early‐Stage Diabetic Kidney Disease and Mitophagy: Focus on Cardiolipin DOI Creative Commons
Zhijie Li, Hongmiao Wang, Nan Liu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(3)

Published: Feb. 1, 2025

ABSTRACT Lipotoxicity plays a crucial role in the progression of diabetic kidney disease (DKD), yet dynamic changes renal lipid composition from diabetes to early‐stage DKD remain unclear. Free fatty acids, lactosylceramides and cardiolipin (CL) were identified as most significantly altered lipids by quantitatively comparing targeted cortex classic spontaneous db/db mice using high‐coverage lipidomics. Further investigation into causes effects decreased CL, which is unique mitochondrial phospholipid, was conducted mitochondria‐rich proximal tubular cells western blotting, real‐time PCR, immunohistochemistry transmission electron microscopy. Reduced expression synthase, key enzyme CL synthesis pathway, inhibition CL‐related mitophagy confirmed under high glucose conditions. In addition, protective effect CL‐targeted Szeto‐Schiller 31 preserving demonstrated both vivo vitro studies. These findings provide new insights pathogenesis perspective offer theoretical basis for discovering treatments.

Language: Английский

Citations

0