Cell Reports, Год журнала: 2025, Номер 44(3), С. 115339 - 115339
Опубликована: Фев. 19, 2025
Язык: Английский
Kidney International, Год журнала: 2024, Номер 106(1), С. 24 - 34
Опубликована: Апрель 16, 2024
Kidney epithelial cells have very high energy requirements, which are largely met by fatty acid oxidation. Complex changes in lipid metabolism observed patients with kidney disease. Defects oxidation and increased uptake, especially the context of hyperlipidemia proteinuria, contribute to this excess build-up exacerbate disease development. Recent studies also highlighted role de novo lipogenesis fibrosis. The defect causes starvation. Increased synthesis, lower can cause toxic build-up, reactive oxygen species generation, mitochondrial damage. A better understanding these metabolic processes may open new treatment avenues for diseases targeting metabolism.
Язык: Английский
Процитировано
24
Nature Reviews Nephrology, Год журнала: 2024, Номер unknown
Опубликована: Сен. 17, 2024
Язык: Английский
Процитировано
20
Antioxidants, Год журнала: 2022, Номер 11(7), С. 1356 - 1356
Опубликована: Июль 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.
Язык: Английский
Процитировано
65
Diabetes, Год журнала: 2022, Номер 71(5), С. 1034 - 1050
Опубликована: Фев. 8, 2022
Mitochondria-associated endoplasmic reticulum membrane (MAM) may have a role in tubular injury diabetic nephropathy (DN), but the precise mechanism remains unclear. Here, we demonstrate that expression of phosphofurin acidic cluster sorting protein 2 (PACS-2), critical regulator MAM formation, is significantly decreased renal tubules patients with DN, and PACS-2 positively correlated function negatively degrees tubulointerstitial lesions. Conditional deletion Pacs-2 proximal (PTs) aggravates albuminuria streptozotocin-induced mouse model diabetes. Mitochondrial fragmentation, disruption, defective mitophagy accompanied by altered mitochondrial dynamics mitophagic proteins, including Drp1 Becn1, are observed mice; these changes more pronounced PT-specific knockout mice. In vitro, overexpression HK-2 cells alleviates excessive fission induced high glucose concentrations through blocking recruitment DRP1 subsequently restores integrity enhances mitophagy. Mechanistically, binds to BECN1 mediates relocalization MAM, where it promotes formation mitophagosome. Together, data highlight an important previously unrecognized ameliorating DN facilitating
Язык: Английский
Процитировано
54
Frontiers in Endocrinology, Год журнала: 2023, Номер 14
Опубликована: Фев. 28, 2023
Renal fibrosis (RF) is the common pathological manifestation of virtually all chronic kidney diseases (CKD) and one major causes end-stage renal disease (ESRD), but pathogenesis which still unclear. tubulointerstitial lesions have been identified as a key hallmark RF pathology. tubular epithelial cells are resident tubulointerstitium play an important role in recovery versus following injury. Studies recent years shown that senescence can accelerate progression fibrosis. Oxidative stress(OS), telomere attrition DNA damage cell senescence. Current interventions therapeutic strategies for cellular include calorie restriction routine exercise, Klotho, senolytics, senostatics, other related drugs. This paper provides overview mechanisms signaling pathways including Wnt/β-catenin/RAS, Nrf2/ARE STAT-3/NF-κB pathway involved therapies targeting future potential patients. These findings may offer promise further treatment CKD.
Язык: Английский
Процитировано
42
Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 17
Опубликована: Авг. 10, 2022
Tubular injury has been shown to play a critical role in the morbidity of diabetic kidney disease (DKD); ferroptosis often occurs tubules during renal development. This study was aimed at evaluating inhibitory effects and potential mechanism dapagliflozin (DAPA) against diabetic-related kidney. C57BL/6 mice were fed high-fat diet (HFD) for 12 weeks, administered small dose streptozocin (STZ) three consecutive days by intraperitoneal injection, then orally (10 mg/kg/day) 8 weeks. Mouse blood urine samples collected, their cortices harvested subsequent investigations. The DAPA also evaluated HK-2 cells subjected simulated conditions through excess glucose or palmitic acid (PA) administration. significantly ameliorated tubular independently glycemic control model mice. In vivo vitro investigations showed that inhibiting ferroptosis. Docking experiments demonstrated SLC40A1 could bind with each other may consequently reduce ubiquitination degradation. conclusion, this study, protective DAPA, irrespective control, observed mouse model. via stabilization, be underlying its action. To best our knowledge, is first investigate treatment DKD.
Язык: Английский
Процитировано
41
Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)
Опубликована: Сен. 14, 2022
Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal (ESRD) worldwide. SGLT2 inhibitors are clinically effective in halting DKD progression. However, underlying mechanisms remain unclear. The serum and kidneys mice with were analyzed using liquid chromatography tandem mass spectrometry (LC–MS/MS)-based metabolomic proteomic analyses. Three groups established: placebo-treated littermate db/m mice, db/db EMPA-treated mice. Empagliflozin (EMPA) placebo (10 mg/kg/d) administered for 12 weeks. EMPA treatment decreased Cys-C urinary albumin excretion compared by 78.60% 57.12%, respectively (p < 0.001 all cases). Renal glomerular area, interstitial fibrosis glomerulosclerosis 16.47%, 68.50% 62.82%, 0.05 Multi-omic analysis revealed that altered protein metabolic profiles group, including 32 proteins, 51 94 metabolites 37 metabolites. Five EMPA-related pathways identified integrating analyses, which involved purine metabolism; pyrimidine tryptophan nicotinate nicotinamide metabolism, glycine, serine threonine metabolism serum. In conclusion, this study demonstrated reprogramming DKD. improved function morphology regulating reprogramming, regulation reductive stress, alleviation mitochondrial dysfunction reduction oxidative stress reaction.
Язык: Английский
Процитировано
41
Cells, Год журнала: 2022, Номер 11(20), С. 3236 - 3236
Опубликована: Окт. 14, 2022
Lipotoxicity is a fundamental pathophysiologic mechanism in diabetes and non-alcoholic fatty liver disease now increasingly recognized diabetic kidney (DKD) pathogenesis. This review highlights lipotoxicity pathways the podocyte proximal tubule cell, which are arguably two most critical sites nephron for DKD. The discussion focuses on membrane transporters lipid droplets, represent potential therapeutic targets, as well current developing pharmacologic approaches to reduce renal lipotoxicity.
Язык: Английский
Процитировано
40
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Июль 17, 2023
Abstract Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, acts as a biomarker for various diseases. However, the exact role underlying mechanism of KIM1 progression AKI remain elusive. Herein, we report that tubular specific knockout Kim1 attenuates cisplatin- or ischemia/reperfusion-induced male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which downregulated AKI, binds to promoter represses its expression. Injury-induced ECD domain death receptor 5 (DR5), activates DR5 following caspase cascade by promoting multimerization, thus induces cell apoptosis exacerbates AKI. Blocking KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against Here, reveal YY1-KIM1-DR5 axis warrants future exploration therapeutic targets.
Язык: Английский
Процитировано
33
Journal of the American Society of Nephrology, Год журнала: 2024, Номер 35(6), С. 795 - 808
Опубликована: Фев. 14, 2024
Kidney injury molecule-1 (KIM-1), also known as T-cell Ig and mucin domain-1 (TIM-1), is a widely recognized biomarker for AKI, but its biological function less appreciated. KIM-1/TIM-1 belongs to the domain family of conserved transmembrane proteins, which bear characteristic six-cysteine Ig-like variable domain. The latter enables binding natural ligand, phosphatidylserine, expressed on surface apoptotic cells necrotic cells. in variety tissues plays fundamental roles regulating sterile inflammation adaptive immune responses. In kidney, KIM-1 upregulated injured renal proximal tubule cells, transforms them into phagocytes clearance dying helps dampen inflammation. TIM-1, T B killer essential cell activation regulatory functions host. Functional polymorphisms gene KIM-1/TIM-1, HAVCR1 , have been associated with susceptibility immunoinflammatory conditions hepatitis A virus-induced liver failure, thought be due differential ability variants bind phosphatidylserine. This review will summarize role health disease potential clinical applications therapeutic target humans.
Язык: Английский
Процитировано
14