Research progress on the treatment of diabetic nephropathy with leech and its active ingredients DOI Creative Commons
Feng Tian,

Xiang Yi,

Feifei Yang

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 26, 2024

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and common cause chronic kidney disease. There currently lack effective treatments for DN, the prognosis patients remains poor. Hirudin, one primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, anti-inflammatory properties, exhibiting significant protective effects on kidneys. In recent years, there has been surge interest in studying potential benefits hirudin, especially its role management DN. This article delves into mechanisms by which hirudin contributes to treatment DN clinical efficacy.

Language: Английский

Pharmacological functions of salidroside in renal diseases: facts and perspectives DOI Creative Commons
Qiong Liu, Jianzhu Chen,

Anqi Zeng

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Rhodiola rosea is a valuable functional medicinal plant widely utilized in China and other Asian countries for its anti-fatigue, anti-aging, altitude sickness prevention properties. Salidroside, most active constituent derived from , exhibits potent antioxidative, hypoxia-resistant, anti-inflammatory, anticancer, anti-aging effects that have garnered significant attention. The appreciation of the pharmacological role salidroside has burgeoned over last decade, making it beneficial option treatment multiple diseases, including atherosclerosis, Alzheimer’s disease, Parkinson’s cardiovascular more. With renoprotective effects, parallel with inhibition oxidative stress inflammation, holds promise as potential therapeutic agent kidney damage. This article provides an overview microinflammatory state disease discuss current strategies, particular focus on highlighting recent advancements utilizing renal disease. mechanisms action are primarily associated regulation gene protein expression glomerular endothelial cells, podocytes, tubule mesangial cells cell carcinoma cell, TNF-α, TGF-β, IL-1β, IL-17A, IL-6, MCP-1, Bcl-2, VEGF, ECM protein, caspase-3, HIF-1α, BIM, well modulation AMPK/SIRT1, Nrf2/HO-1, Sirt1/PGC-1α, ROS/Src/Cav-1, Akt/GSK-3β, TXNIP-NLRP3, ERK1/2, TGF-β1/Smad2/3, PI3K/Akt, Wnt1/Wnt3a β-catenin, TLR4/NF-κB, MAPK, JAK2/STAT3, SIRT1/Nrf2 pathways. To best our knowledge, this review first to comprehensively cover protective diverse suggests great be developed drug metabolic syndrome, cerebrovascular diseases complications.

Language: Английский

Citations

14
Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy DOI Creative Commons
Hong Jiang,

Zhirang Shen,

Jing Zhuang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial are challenging to regenerate once injured. They essential for maintaining integrity barrier. Damage resulting from intrinsic or extrinsic factors, leads proteinuria early stages eventually progresses chronic disease (CKD). Immune-mediated podocyte injury is primary pathogenic mechanism proteinuric diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis with involvement. An extensive body evidence indicates that podocytes not only contribute significantly maintenance barrier serve as targets immune responses but also exhibit cell-like characteristics, participating both innate adaptive immunity. play mediating represent potential therapeutic CKD. This review aims systematically elucidate mechanisms various lesions provide an overview recent advances immunotherapy. It offers valuable insights deeper understanding identification new targets, has significant implications future clinical diagnosis treatment podocyte-related disorders.

Language: Английский

Citations

10
Role of pyruvate kinase M2-mediated metabolic reprogramming during podocyte differentiation DOI Creative Commons
Qi Yuan, Jiao Miao, Qianqian Yang

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(5)

Published: May 11, 2020

Abstract Podocytes, a type of highly specialized epithelial cells, require substantial levels energy to maintain glomerular integrity and function, but little is known on the regulation podocytes’ energetics. Lack metabolic analysis during podocyte development led us explore distribution mitochondrial oxidative phosphorylation glycolysis, two major pathways cell metabolism, in cultured podocytes vitro differentiation. Unexpectedly, we observed stronger glycolytic profile, accompanied by an increased complexity differentiated podocytes, indicating that mature boost both glycolysis metabolism meet their augmented demands. In addition, found shift predominant source from anaerobic immature differentiation process. Furthermore, identified crucial regulator for development, pyruvate kinase M2. Pkm2 -knockdown showed dramatic reduction resulting defects Meanwhile, podocyte-specific -knockout (KO) mice developed worse albuminuria injury after adriamycin treatment. We mammalian target rapamycin (mTOR) as critical PKM2 development. Pharmacological inhibition mTOR potently abrogated expression disrupted differentiation, existence checkpoint need be satisfied order allow

Language: Английский

Citations

60
M2 macrophage‐derived exosomal miR‐25‐3p improves high glucose‐induced podocytes injury through activation autophagy via inhibiting DUSP1 expression DOI Open Access

Haihua Huang,

Huiyun Liu,

Jiazhen Tang

et al.

IUBMB Life, Journal Year: 2020, Volume and Issue: 72(12), P. 2651 - 2662

Published: Oct. 26, 2020

Abstract Diabetic nephropathy (DN) is the primary reason of chronic kidney disease. The aim our study to explore role and action mechanism M2 macrophage‐derived exosomes in high glucose (HG)‐induced podocytes injury. Here, 30 mmol/L HG was used induce Annexin V‐FITC/PI double staining performed measure apoptosis, western blot carried out ensure proteins expression. shape identified using TEM. Besides, expression miR‐25‐3p determined by qRT‐PCR, FAM‐labeled miR‐25‐5p combined with DiI‐labeled were utilized uptake exosomes. Relationship between DUSP family members ensued luciferase activity assay. In beginning, we found that macrophage ameliorated HG‐induced apoptosis epithelial‐mesenchymal transition through secreting Subsequently, highly expressed effectively improved Furthermore, inhibition inefficiently repressed injury, thus proposed attenuated injury exosomal miR‐25‐3p. Then, an autophagy inhibitor stimulate podocytes, demonstrated activating autophagy. Finally, DUSP1 proved be a downstream target mediated Our results indicated could improve via activate cells suppressing We newly potential therapy strategy for DN treatment.

Language: Английский

Citations

56
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
Biomimetic models of the glomerulus DOI
Marta G. Valverde, Luis Santiago Mille, Kianti P. Figler

et al.

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(4), P. 241 - 257

Published: Jan. 21, 2022

Language: Английский

Citations

35
Transcriptional and functional motifs defining renal function revealed by single-nucleus RNA sequencing DOI Creative Commons
Jun Xu, Yifang Liu, Hongjie Li

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(25)

Published: June 13, 2022

Recent advances in single-cell sequencing provide a unique opportunity to gain novel insights into the diversity, lineage, and functions of cell types constituting tissue/organ. Here, we performed single-nucleus study adult Drosophila renal system, consisting Malpighian tubules nephrocytes, which shares similarities with mammalian kidney. We identified 11 distinct clusters representing stem cells, stellate regionally specific principal garland nephrocyte pericardial nephrocytes. Characterization transcription factors each cluster fruitless ( fru ) as playing role regeneration Hepatocyte nuclear factor 4 Hnf4 regulating glycogen triglyceride metabolism. In addition, number genes, including Rho guanine nucleotide exchange at 64C RhoGEF64c ), Frequenin 2 Frq2 Prip , CG1093 that are involved unusual star shape cells. Importantly, dataset allows visualization expression organ level genes ion transport junctional permeability, providing systems-level view organization physiological roles tubules. Finally, cross-species analysis allowed us match fly kidney mouse planarian protonephridia, knowledge will help generation disease models. Altogether, our provides comprehensive resource for studying

Language: Английский

Citations

34
Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens DOI Creative Commons
Dominik Kylies, Marina Zimmermann, Fabian Haas

et al.

Nature Nanotechnology, Journal Year: 2023, Volume and Issue: 18(4), P. 336 - 342

Published: April 1, 2023

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited systems1. However, optimal performance is usually reached laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only light-emitting diode (LED)-based widefield systems. As a possible alternative, computational method for image enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. this not explored pathology date, because on own, it does sufficient routine use. Here, we report expansion-enhanced (ExSRRF), simple, robust, scalable and accessible workflow that provides of up 25 nm LED-based microscopy. ExSRRF enables molecular profiling subcellular structures from archival formalin-fixed paraffin-embedded tissues complex experimental specimens, including ischaemic, degenerative, neoplastic, genetic immune-mediated disorders. Furthermore, examples potential application show can be used identify quantify classical features endoplasmic reticulum stress the murine ischaemic kidney diagnostic ultrastructural human biopsies.

Language: Английский

Citations

21
New insights into the immune functions of podocytes: the role of complement DOI Creative Commons
Valentina Bruno,

Anne K. Mühlig,

Jun Oh

et al.

Molecular and Cellular Pediatrics, Journal Year: 2023, Volume and Issue: 10(1)

Published: April 15, 2023

Abstract Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition their adhesive properties in maintaining integrity barrier, they have other functions, such as synthesis components basement membrane (GBM), production vascular endothelial growth factor (VEGF), release inflammatory proteins, and expression complement components. They also participate crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming β (TGFβ), bone morphogenetic protein 7 (BMP-7), latent β-binding 1 (LTBP1), extracellular vesicles. Growing literature suggests that podocytes share many innate adaptive immunity, supporting multifunctional ensuring healthy glomerulus. As consequence, “immune podocyte” dysfunction is thought be involved pathogenesis several diseases, referred “podocytopathies.” Multiple factors like mechanical, oxidative, and/or immunologic stressors can induce cell injury. The system, part both define podocyte damage by mechanisms, reactive oxygen species (ROS) generation, cytokine production, endoplasmic reticulum stress, ultimately affecting cytoskeleton, with subsequent detachment from GBM onset proteinuria. Interestingly, found source target complement-mediated express proteins contribute local activation. At same time, rely on protective mechanisms escape this damage. H (CFH), one main regulators cascade, well membrane-bound CD46 or cofactor (MCP), CD55 decay-accelerating (DAF), CD59 defensin. Further autophagy actin-based endocytosis, homeostasis protection against This review will provide overview immune functions response immune-mediated injury, focusing pathogenic link between

Language: Английский

Citations

21
Targeting HMGB1: A Potential Therapeutic Strategy for Chronic Kidney Disease DOI Creative Commons
Tongtong Liu, Qian Li, Jin Qi

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(15), P. 5020 - 5035

Published: Jan. 1, 2023

High-mobility group protein box 1 (HMGB1) is a member of highly conserved high-mobility present in all cell types.HMGB1 plays multiple roles both inside and outside the cell, depending on its subcellular localization, context, post-translational modifications.HMGB1 also associated with progression various diseases.Particularly, HMGB1 critical role CKD prognosis.HMGB1 participates key events by activating downstream signals, including renal inflammation, onset persistent fibrosis, aging, AKI-to-CKD transition, important cardiovascular complications.More importantly, distinct chronic pathophysiology kidney disease, which differs from that acute lesions.This review describes regulatory homeostasis summarizes how affects prognosis.Finally, some promising therapeutic strategies for targeted inhibition improving are summarized.Although application as target faces challenges, more in-depth understanding intracellular extracellular mechanisms underly occurrence might render an attractive CKD.

Language: Английский

Citations

19