Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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Static magnetic fields alleviate diabetic nephropathy by reducing renal cell inflammation and promoting M2 macrophage polarization

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: Feb. 27, 2025

Abstract Diabetic nephropathy (DN) is one of the most severe diabetic complications, which can easily progress into irreversible and detrimental end‐stage renal disease if not properly controlled. However, effective prevention DN progression has always remained a huge challenge. Moderate intensity static magnetic fields (SMFs), have advantages non‐invasive high penetration, shown beneficial effects in reducing blood glucose type 2 diabetes mice recent years. In this study, by using both db/db high‐fat diet streptozotocin‐induced moderate mice, we found that SMFs significant on compared to control. Further analyzing with diabetes, kidney inflammation, vascular abnormalities, fibrosis were all greatly reduced. Moreover, promote macrophages polarized M2. vitro cellular experiments also demonstrate positive cell as well increasing M2 macrophage polarization promoting F‐actin assembly. Therefore, our results show great potential be developed new physical modality used treatment DN, possibly other types chronic diseases.

Language: Английский

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Metabolomics Based Exploration of the Mechanism of Action of Tripterygium Glycosides in Diabetic Kidney Disease

Biomedical Chromatography, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 31, 2025

ABSTRACT Tripterygium glycosides (TGs), the primary active components of wilfordii , have demonstrated therapeutic efficacy in treating diabetic kidney disease (DKD). However, precise mechanisms underlying their action remain elusive, limiting full realization medicinal potential. This study employed serum metabolomics based on liquid chromatography–mass spectrometry (LC‐MS) analysis to elucidate by which TGs combat DKD. We evaluated protective effects DKD following treatment. Serum samples were collected before and after treatment, metabolic profiles analyzed using LC‐MS. Our revealed that significantly modulated hedgehog signaling pathway, a key pathway implicated pathogenesis. represents first comprehensive investigation pathways regulated context approach. findings provide robust theoretical foundation for more effective utilization potential combination therapies involving management These insights pave way further research development targeted strategies this challenging condition.

Language: Английский

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IL-6 and diabetic kidney disease

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

Published: Dec. 19, 2024

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes associated with high mortality and disability rates. Inflammation has emerged as key pathological mechanism in DKD, prompting interest novel therapeutic approaches targeting inflammatory pathways. Interleukin-6 (IL-6), well-established cytokine known for mediating various responses, attracted great attention the DKD field. Although multiple

Language: Английский

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Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3646 - 3646

Published: April 12, 2025

Renal inflammatory diseases are a group of severe conditions marked by significant morbidity and mortality. Extracellular vesicles (EVs), as facilitators intercellular communication, have been recognized pivotal regulators renal diseases, significantly contributing to these modulating immune responses among other mechanisms. This review highlights the intricate mechanisms through which EVs modulate macrophage-kidney cell interactions regulating macrophages, principal cells within milieu. regulation subsequently influences pathophysiology such acute kidney injury chronic disease. Furthermore, understanding offers novel opportunities alleviate consequences associated with diseases. In addition, we summarize therapeutic landscape based on EV-mediated macrophage regulatory mechanisms, highlighting potential biomarkers targets well challenges limitations translating therapies into clinical practice.

Language: Английский

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Association of inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy: a bidirectional Mendelian randomization study

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Nov. 7, 2024

Objective Previous observational studies have suggested associations between various inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy. However, the causal association remains uncertain. Method Summary statistics for nephropathy were obtained from a publicly available genome-wide study. Data on sourced study protein quantitative trait loci. The inverse variance-weighted method was applied as primary inference. MR-Egger, weighted mode, median employed supplementary analyses. Sensitivity analyses performed to detect heterogeneity potential horizontal pleiotropy in Result Genetic evidence indicated that elevated levels of fibroblast growth factor 19 promoted occurrence mellitus, increased concentrations 21 levels, C-C motif chemokine eotaxin interleukin-10 mitigated risk developing while did not exert significant influence said proteins. Elevated tumor necrosis ligand superfamily member 14 TNF-related activation-induced cytokine associated an nephropathy, interleukin-1-alpha transforming factor-alpha potentially correlated diminished further ensure robustness our findings. Conclusion Mendelian randomization analysis highlights offering valuable reference future research.

Language: Английский

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Fiery Connections: Macrophage-Mediated Inflammation, the Journey from Obesity to Type 2 Diabetes Mellitus and Diabetic Kidney Disease

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2209 - 2209

Published: Sept. 27, 2024

The high prevalence of diabetes mellitus (DM) poses a significant public health challenge, with diabetic kidney disease (DKD) as one its most serious consequences. It has become increasingly clear that type 2 DM (T2D) and the complications DKD are not purely metabolic disorders. This review outlines emerging evidence related to step-by-step contribution macrophages development progression in individuals who specifically develop T2D result obesity. macrophage is prominent inflammatory cell contributes obesity, where adipocyte hypertrophy leads recruitment eventually expansion adipose tissue. recruited secrete proinflammatory cytokines, which cause systemic inflammation, glucose dysregulation, insulin sensitivity, ultimately contributing T2D. Under such pathological changes, susceptible elevated thereby activates signaling pathways drive monocyte recruitment. In particular, early produces cytokines/chemokines contribute inflammation tissue damage associated pathology. Macrophage activation crucial inciting factors also persist progresses. Thus, targeting function could be promising therapeutic approach, potentially offering benefits for managing at all stages progression.

Language: Английский

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Combining bioinformatics and network pharmacology to explore diagnostic biomarkers and mechanisms associated with mitochondria in diabetic nephropathy using Rhodiola Rosea

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

This study aimed to explore diagnostic biomarkers associated with mitochondria in the treatment of diabetic nephropathy (DN) using Rhodiola Rosea (RR) and elucidate underlying regulatory mechanisms. The target genes corresponding active ingredients RR, mitochondria-related genes, DN-related were intersected differentially expressed from GSE96804 obtain pharmacopoeia (MRPGs). Based on these a pharmacological network was constructed. Additionally, biological pathways enriched by biomarkers, their correlation DN immune infiltration profile, binding ability RR analyzed. A total 24 MRPGs against identified Venn analysis. Subsequently, six screened machine learning, namely CAT, CASP3, CPT1A, OGDH, CYP27B1, ALDH9A1. Immune analysis showed eight differential cells between control groups, macrophages M2 neutrophils correlating all biomarkers. molecular docking, two targeting relationship pairs identified: CAT-RUTIN ALDH9A1-RUTIN-2, both demonstrating good capacity. for based effects mitochondrial function. findings revealed components potential therapeutic mechanisms treating DN.

Language: Английский

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