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

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(12)

Опубликована: Дек. 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.

Язык: Английский

Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment DOI Creative Commons
Rüssel J. Reiter, Ramaswamy Sharma, Walter Manucha

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480

Опубликована: Сен. 3, 2024

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.

Язык: Английский

Процитировано

14
Acute Effect of High Fat Intake on Urinary Acidification Parameters DOI Creative Commons
Seyed Alireza Zomorodian, Xilong Li,

John Poindexter

и другие.

Kidney International Reports, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease DOI Creative Commons
Swayam Prakash Srivastava, Han Zhou,

Rachel Shenoi

и другие.

Science Advances, Год журнала: 2024, Номер 10(49)

Опубликована: Дек. 4, 2024

Angiopoietin-like 4 (ANGPTL4), a key protein involved in lipoprotein metabolism, has diverse effects. There is an association between Angptl4 and diabetic kidney disease; however, this not been well investigated. We show that both podocyte- tubule-specific ANGPTL4 are crucial fibrogenic molecules diabetes. Diabetes accelerates the phenotype control mice but mutant mice. The protective effect observed correlated with reduction stimulator of interferon genes pathway activation, expression pro-inflammatory cytokines, reduced epithelial-to-mesenchymal transition endothelial-to-mesenchymal transition, lessened mitochondrial damage, increased fatty acid oxidation. Mechanistically, we demonstrate or tubule-secreted interacts Integrin β1 influences dipeptidyl-4 β1. utility targeted pharmacologic therapy specifically inhibits gene kidneys protects from proteinuria fibrosis. Together, these data tubule-derived kidneys.

Язык: Английский

Процитировано

6
Protein handling in kidney tubules DOI
Andrew M. Hall

Nature Reviews Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Язык: Английский

Процитировано

0
Renal tubular S100A7a impairs fatty acid oxidation and exacerbates renal fibrosis via both intracellular and extracellular pathway DOI

Pengxiao Sun,

Qingzhou Chen,

Xiaomei Chen

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(3), С. 167656 - 167656

Опубликована: Янв. 6, 2025

Язык: Английский

Процитировано

0
Boeravinone C ameliorates lipid accumulation and inflammation in diabetic kidney disease by activating PPARα signaling DOI

Zhuoqing Cheng,

Honghong Zhan,

Han Yuan

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119398 - 119398

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Galloflavin mitigates acute kidney injury by suppressing LDHA-dependent macrophage glycolysis DOI Creative Commons

Jie Wei,

Xinyu Chen, Zhijuan Wang

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 150, С. 114265 - 114265

Опубликована: Фев. 16, 2025

Macrophage-mediated inflammation is closely linked to the pathogenesis of acute kidney injury (AKI) and shift macrophages a pro-inflammatory phenotype being reliant on glycolytic metabolism. Galloflavin, polyphenol derived from tea, functions as lactate dehydrogenase A (LDHA) inhibitor, effectively obstructing metabolic pathways. However, specific immunometabolic regulatory galloflavin in remain unclear. Here, we observed that drives alleviation metabolism levels lipopolysaccharide (LPS)-induced (RAW264.7 cells human peripheral blood mononuclear cells-derived macrophages) through downregulation LDHA expression, thereby inhibiting macrophage conversion reducing release inflammatory cytokines. overexpression counteracts effects macrophages. In addition, vivo experiments protective effect against cecal ligation puncture (CLP) cisplatin-induced renal injury. The ability inhibit glycolysis macrophages, regulating their phenotypic transition during AKI was further validated isolation primary This intervention ultimately ameliorated response decelerated progression AKI. Collectively, confers protection by suppressing LDHA-dependent mechanism, positioning it potential therapeutic option for future.

Язык: Английский

Процитировано

0
Huangqi and Danshen improve the chronic nephrotoxicity of Cyclosporin A by regulating lipid metabolism DOI Creative Commons
Ranran Gao, Cong Han,

Gui-yuan Sui

и другие.

Phytomedicine, Год журнала: 2025, Номер 140, С. 156582 - 156582

Опубликована: Фев. 26, 2025

The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role CsA nephrotoxicity not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza (HD) ameliorating the CsA, mechanisms still need be fully clarified. This study innovatively aimed analyse coexpression proteins serum metabolites for identification key pathways targets. provides novel insight into mechanism by which HD ameliorates CsA-induced We utilized intervene both vivo vitro models induced CsA. For experiments, we constructed a network metabolites, was used screen pathways. To validate these findings, knocked down vivo. studies, employed MTT, Transwell, flow cytometry, immunofluorescence assays monitor epithelial-mesenchymal transition (EMT) HK-2 cells. Additionally, electron microscopy Seahorse examine effects on mitochondrial structure function. Furthermore, overexpressed Ppara further confirm improves can improve pathological damage function; regulate blood lipids, inflammation oxidative stress indicators; reduce apoptosis tissues. Joint protein metabolomics analyses revealed that two lipid metabolism-related (the PPAR signalling pathway linoleic acid pathway) were coenriched, involving six differential (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, Pck1) differentially abundant (alpha-Dimorphecolic 12,13-EpOME). Western blot verify expressed proteins. improved accumulation, as demonstrated transmission (TEM) analysis Oil Red O staining. Knockdown affected expression ACOX1 exacerbated RF. In verification significantly inhibited EMT cells overexpression promoted HD-mediated regulation function, reduced apoptosis, ameliorate through protein-serum coexpression, pathway, metabolism. HD-induced upregulation metabolism, function are mechanisms. Ppara/ACOX1/TGF-β1 axis may an this process. These findings offer potential targets future development therapeutic strategies drugs.

Язык: Английский

Процитировано

0
Lipidomics reveals potential biomarkers and pathophysiological insights in the progression of diabetic kidney disease DOI Creative Commons

Xiaozhen Guo,

Zixuan Zhang,

Cuina Li

и другие.

Metabolism Open, Год журнала: 2025, Номер 25, С. 100354 - 100354

Опубликована: Март 1, 2025

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, affecting over 30 % diabetes mellitus (DM) patients. Early detection DKD in DM patients can enable timely preventive therapies, and potentially delay progression. Since relies on fatty acid oxidation for energy, dysregulated lipid metabolism has been implicated proximal tubular cell damage pathogenesis. This study aimed to identify alterations during development potential biomarkers differentiating from DM. lipidomics analysis was performed serum collected 55 with DM, 21 early stage 32 advanced DKD, 22 healthy subjects. Associations between lipids risk were evaluated by logistic regression. Lipid profiling revealed elevated levels certain lysophosphatidylethanolamines (LPEs), phosphatidylethanolamines (PEs), ceramides (Cers), diacylglycerols (DAGs) DM-DKD transition, while most LPEs, lysophosphatidylcholines (LPCs), along several monoacylglycerol (MAG) triacylglycerols (TAGs), increased further DKD-E DKD-A. Logistic regression indicated positive associations LPCs, PEs, DAGs risk, LPEs correlating significantly urinary albumin-to-creatinine ratio (UACR) inversely estimated glomerular filtration rate (eGFR). A machine-learning-derived biomarker panel, Lipid9, consisting LPC(18:2), LPC(20:5), LPE (16:0), (18:0), (18:1), (24:0), PE (34:1), (34:2), (36:2), accurately distinguished (AUC: 0.78, 95 CI 0.68-0.86) Incorporating two clinical indexes, creatinine blood urea nitrogen, Lipid9-SCB model improved 0.83, 0.75-0.90) notably more sensitive identifying 0.79, 0.67-0.91). deciphers signature progression, suggests panel as a promising tool

Язык: Английский

Процитировано

0
ECHS1 as a Lipid Metabolism Biomarker for Pediatric Focal Segmental Glomerulosclerosis DOI Creative Commons
Chao He, Wei Peng, Sheng Li

и другие.

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0319049 - e0319049

Опубликована: Март 10, 2025

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and often leads to end-stage renal disease. However, the underlying pathophysiological mechanisms that contribute disease progression require further investigation establish appropriate therapeutic targets biomarkers. This study aimed clarify molecular FSGS by focusing on differentially expressed genes (DEGs) lipid metabolism-related (LMRGs). We utilized GSE69814, GSE129973, GSE121233 datasets, which comprise glomerular transcriptomes from patients with FSGS, minimal change (MCD), unaffected kidney tissues. identified 2,459 DEGs GSE69814 dataset 982 GSE129973 dataset. These intersected 1,450 LMRGs, resulting in 56 LMRGs (DELMRGs). Enrichment analysis revealed these DELMRGs were primarily involved fatty acid metabolic processes; localized microbodies, peroxisomes, mitochondrial matrices; exhibited oxidoreductase activity. Protein-protein interaction networks constructed using Cytoscape, five hub (enoyl-CoA hydratase, short chain 1 [ ECHS1 ] , EHHADH, IDH1, SUCLG1 ALDH3A2 ) multiple algorithms. assessed diagnostic performance receiver operating characteristic curves expression levels dataset, found showed strong potential. Immunohistochemical verification clinical specimens children confirmed significant compared normal MCD highlights as potential biomarker for pediatric suggesting role early diagnosis or personalized treatment, offering insights into its pathogenesis paving way targeted strategies.

Язык: Английский

Процитировано

0