Targeting lipid metabolic reprogramming to alleviate diabetic kidney disease: molecular insights and therapeutic strategies DOI Creative Commons
Wei Yu, Haoyu Yang, Zhou Ling

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Diabetic kidney disease (DKD) is one of the major complications diabetes, and its pathological progression closely associated with lipid metabolic reprogramming. Under diabetic conditions, renal cells undergo significant abnormalities, including increased uptake, impaired fatty acid oxidation, disrupted cholesterol efflux, enhanced catabolism, as adaptive responses to stress. These changes result in accumulation lipids such free acids, diacylglycerol, ceramides, leading lipotoxicity that triggers inflammation fibrosis. Hypoxia DKD microenvironment suppresses oxidation promotes synthesis through HIF-1α pathway, while chronic exacerbates disturbances via inflammatory cytokines, inflammasomes, macrophage polarization. Targeting metabolism represents a promising therapeutic strategy for alleviating DKD; however, further clinical translational studies are warranted validate efficacy safety these approaches.

Language: Английский

Podocytopathies DOI Open Access
Jeffrey B. Kopp, Hans‐Joachim Anders, Katalin Suszták

et al.

Nature Reviews Disease Primers, Journal Year: 2020, Volume and Issue: 6(1)

Published: Aug. 13, 2020

Language: Английский

Citations

357
Molecular consequences of SARS-CoV-2 liver tropism DOI Creative Commons
Nicola Wanner, Geoffroy Andrieux, Pau Badia-i-Mompel

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(3), P. 310 - 319

Published: March 28, 2022

Extrapulmonary manifestations of COVID-19 have gained attention due to their links clinical outcomes and potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart kidney. Whether it also directly affects liver has been debated2,3. Here we provide clinical, histopathological, molecular bioinformatic evidence for hepatic SARS-CoV-2. We find that injury, indicated by a high frequency abnormal function tests, is common feature in two independent cohorts patients with requiring hospitalization. Using autopsy samples obtained from third patient cohort, multiple levels SARS-CoV-2 tropism, viral RNA detection 69% specimens, successful isolation infectious tissue postmortem. Furthermore, identify transcription-, proteomic- transcription factor-based activity profiles samples, revealing similarities signatures associated other infections human liver. Together, comprehensive multimodal analysis which increases our understanding consequences severe could be useful identification organ-specific pharmacological targets.

Language: Английский

Citations

139
Diabetes mellitus—Progress and opportunities in the evolving epidemic DOI
E. Dale Abel, Anna L. Gloyn, Carmella Evans‐Molina

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3789 - 3820

Published: July 1, 2024

Language: Английский

Citations

34
Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review DOI Creative Commons

Shiwan Hu,

Hang Xing, Yu Wei

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 19, 2024

Diabetic kidney disease (DKD) is a long-term and serious complication of diabetes that affects millions people worldwide. It characterized by proteinuria, glomerular damage, renal fibrosis, leading to end-stage disease, the pathogenesis complex involves multiple cellular molecular mechanisms. Among three kinds intraglomerular cells including podocytes, endothelial (GECs) mesangial (MCs), alterations in one cell type can produce changes others. The cell-to-cell crosstalk plays crucial role maintaining filtration barrier (GFB) homeostasis. In this review, we summarized recent advances understanding pathological interactions these types DKD then focused on signaling pathways factors mediate crosstalk, such as angiopoietins, vascular growth factors, transforming factor-β, Krüppel-like retinoic acid receptor response protein 1 exosomes, etc. Furthermore, also simply introduce application latest technologies studying within new promising mediators for DKD. conclusion, review provides comprehensive updated overview highlights its importance development novel intervention approaches.

Language: Английский

Citations

26
Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases DOI
Christopher Huynh,

Jaewhee Ryu,

Jooho Lee

et al.

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 19(2), P. 102 - 122

Published: Nov. 24, 2022

Language: Английский

Citations

51
Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy DOI Creative Commons
Fabian Braun, Ahmed H. Abed,

Dominik Sellung

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(11)

Published: April 4, 2023

Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in reversal end-organ damage, like kidney injury and chronic disease, remains unclear. In this study, ultrastructural analysis serial human biopsies showed that long-term use ERT reduced Gb3 podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9-mediated α-galactosidase knockout cell line confirmed ERT-mediated without resolution Transcriptome-based connectivity mapping SILAC-based quantitative proteomics identified α-synuclein (SNCA) as key event mediating Genetic pharmacological inhibition SNCA improved structure function podocytes, exceeding benefits ERT. Together, work reconceptualizes Fabry-associated beyond accumulation, introduces modulation potential intervention, especially patients with nephropathy.

Language: Английский

Citations

29
Role of biophysics and mechanobiology in podocyte physiology DOI
Jonathan C. Haydak, Evren U. Azeloglu

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(6), P. 371 - 385

Published: March 5, 2024

Language: Английский

Citations

16
Roles of mTOR in Diabetic Kidney Disease DOI Creative Commons

Mako Yasuda‐Yamahara,

Shinji Kume, Hiroshi Maegawa

et al.

Antioxidants, Journal Year: 2021, Volume and Issue: 10(2), P. 321 - 321

Published: Feb. 22, 2021

Diabetic kidney disease (DKD) is the leading cause of end-stage renal and number patients affected increasing worldwide. Thus, there a need to establish new treatment for DKD improve prognosis diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in pathogenesis DKD. In particular, activity mechanistic target rapamycin complex 1 (mTORC1), nutrient-sensing signaling molecule, hyperactivated various organs patients, which suggests involvement excessive mTORC1 activation diabetes. DKD, may be podocyte damage, causes proteinuria, tubular cell injury decreases function. Therefore, elucidating role developing therapeutic agents suppress hyperactivity shed light on treatments future.

Language: Английский

Citations

43
Podocyte Aging: Why and How Getting Old Matters DOI Open Access
Stuart J. Shankland, Yuliang Wang, Andréy S. Shaw

et al.

Journal of the American Society of Nephrology, Journal Year: 2021, Volume and Issue: 32(11), P. 2697 - 2713

Published: Oct. 29, 2021

The effects of healthy aging on the kidney, and how these intersect with superimposed diseases, are highly relevant in context population's increasing longevity. Age-associated changes to podocytes, which terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses molecular cellular mechanisms underlying podocyte aging, might be augmented by disease aged approaches mitigate progressive damage podocytes. Furthermore, we address biologic pathways such as those associated growth confound humans rodents.

Language: Английский

Citations

42
Kaempferol attenuated diabetic nephropathy by reducing apoptosis and promoting autophagy through AMPK/mTOR pathways DOI Creative Commons

Hongqin Sheng,

Duo Zhang, Jiaqi Zhang

et al.

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 30, 2022

Renal podocyte injury, apoptosis and autophagy are involved in the occurrence development of diabetic nephropathy (DN). Kaempferol (KPF) has promotion inhibition properties miscellaneous diseases, but these functions DN have not yet been elucidated.We used db/db mice to evaluate protective role KPF on DN. The anti-DN effect was evaluated by urine albumin-to-creatinine ratio pathological changes kidney tissue. Injury podocytes observed through Transmission electron microscopy. Immunofluorescence, Western blot, Immunohistochemistry were detect protein expression podocyte-associated molecules, autophagy, AMPK/mTOR pathway.We demonstrated that treatment significantly attenuated diabetes-induced albuminuria glycolipid metabolism dysfunction. In addition, alleviated mesangial matrix expansion, glomerular basement membrane thickening loss or fusion podocytes. Mechanistically, regulated autophagic proteins (upregulated LC3II, Beclin-1, Atg7 Atg 5, downregulated p62/SQSTM1), accompanied inhibited renal (downregulated Caspase 3 Bax, upregulated Bcl-2). could regulate signaling pathways increasing p-AMPK decreasing p-mTOR expressions.In conclusion, might a reduced enhanced which correlated with regulating pathways.

Language: Английский

Citations

33