Nano Today, Journal Year: 2024, Volume and Issue: 61, P. 102624 - 102624
Published: Dec. 31, 2024
Language: Английский
MedComm, Journal Year: 2024, Volume and Issue: 5(8)
Published: Aug. 1, 2024
Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.
Language: Английский
Citations
28
Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)
Published: May 13, 2024
Abstract Macrophages are exceptionally diversified cell types and perform unique features functions when exposed to different stimuli within the specific microenvironment of various kidney diseases. In instances tissue necrosis or infection, patterns associated with damage pathogens prompt development pro-inflammatory macrophages (M1). These M1 contribute exacerbating damage, inflammation, eventual fibrosis. Conversely, anti-inflammatory (M2) arise in same circumstances, contributing repair regeneration processes. Impaired causes fibrosis, hence play a protective pathogenic role. response harmful body, inflammasomes, complex assemblies multiple proteins, assume pivotal function innate immunity. The initiation inflammasomes triggers activation caspase 1, which turn facilitates maturation cytokines, death. kidneys possess complete elements NLRP3 inflammasome, including NLRP3, ASC, pro-caspase-1. When activated, it caspase-1, resulting release mature proinflammatory cytokines (IL)-1β IL-18 cleavage Gasdermin D (GSDMD). This process therefore then induces pyroptosis, leading renal death, dysfunction. NLRP3–ASC–caspase-1–IL-1β–IL-18 pathway has been identified as factor pathophysiology numerous this review, we explore current progress understanding macrophage behavior concerning injury, fibrosis kidneys. Emphasizing role activated both advancement recovery phases diseases, article delves into potential strategies modify functionality also discusses emerging approaches selectively target their signaling components kidney, aiming facilitate healing
Language: Английский
Citations
18
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4350 - 4350
Published: April 15, 2024
Diabetes is not solely a metabolic disorder but also involves inflammatory processes. The immune response it incites primary contributor to damage in target organs. Research indicates that during the initial phases of diabetic nephropathy, macrophages infiltrate kidneys alongside lymphocytes, initiating cascade reactions. interplay between and other renal cells pivotal advancement kidney disease within hyperglycemic milieu. While M1 react stimuli induced by elevated glucose levels early progression, their subsequent transition M2 macrophages, which possess anti-inflammatory tissue repair properties, contributes fibrosis later stages nephropathy transforming into myofibroblasts. Comprehending diverse functions regulating activity could offer therapeutic benefits for managing this condition.
Language: Английский
Citations
8
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117079 - 117079
Published: July 4, 2024
Macrophages are widely distributed throughout various tissues of the body, and mounting evidence suggests their involvement in regulating tissue microenvironment, thereby influencing disease onset progression through direct or indirect actions. In chronic kidney (CKD), disturbances renal functional homeostasis lead to inflammatory cell infiltration, tubular expansion, glomerular atrophy, subsequent fibrosis. play a pivotal role this pathological process. Therefore, understanding is imperative for investigating CKD progression, mitigating its advancement, offering novel research perspectives fibrosis treatment from an immunological standpoint. This review primarily delves into intrinsic characteristics macrophages, origins, diverse subtypes, associations with Particular emphasis placed on transition between M1 M2 phenotypes. late-stage CKD, there shift phenotype, accompanied by increased prevalence macrophages. governed activation TGF-β1/SMAD3 JAK/STAT pathways, which facilitate macrophage-to-myofibroblast (MMT). The tyrosine kinase Src involved both signaling cascades. By thoroughly elucidating macrophage functions comprehending modes molecular mechanisms macrophage-fibroblast interaction kidney, novel, tailored therapeutic strategies preventing attenuating can be developed.
Language: Английский
Citations
8
Bioactive Materials, Journal Year: 2024, Volume and Issue: 41, P. 193 - 206
Published: July 20, 2024
Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives phenotypic polarization (M0 M1, then M2) was constructed by integrating anti-inflammatory components proinflammatory solvents.
Language: Английский
Citations
8
Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(2)
Published: March 1, 2024
Abstract Systemic lupus erythematosus (SLE) is known as an autoimmune disorder that characterized by the breakdown of self‐tolerance, resulting in disease onset and progression. Macrophages have been implicated a factor development SLE through faulty phagocytosis dead cells or imbalanced M1/M2 ratio. The study aimed to investigate immunomodulatory effects Lactobacillus delbrueckii rhamnosus on M1 M2 macrophages new case patients. For this purpose, blood monocytes were collected from patients healthy people cultured for 5 days produce macrophages. 48 h, then cocultured with either probiotics lipopolysaccharides (LPS). Flow cytometry real‐time polymerase chain reaction used analyze expression cluster differentiation (CD) 14, CD80, human leukocyte antigen – DR (HLADR) markers, well cytokine (interleukin [IL]1‐β, IL‐12, tumor necrosis α [TNF‐α], IL‐10, transforming growth beta [TGF‐β]). results indicated three distinct macrophage populations, M0, M1, M2. In both control patient‐derived macrophage‐derived (MDMs), probiotic groups showed decrease CD14, HLADR compared LPS group. This was particularly evident M0 subjects. addition, increased levels IL‐10 TGF‐β decreased IL1‐β, TNF‐α MDMs subjects groups. Although there higher pro‐inflammatory cytokines patients, anti‐inflammatory general, L. could induce
Language: Английский
Citations
6
Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(4), P. 3134 - 3163
Published: April 4, 2024
This review focuses on the thioredoxin domain containing 5 (TXNDC5), also known as endoplasmic reticulum protein 46 (ERp46), a member of disulfide isomerase (PDI) family with dual role in multiple diseases. TXNDC5 is highly expressed endothelial cells, fibroblasts, pancreatic β-cells, liver and hypoxic tissues, such cancer cells atherosclerotic plaques. plays crucial regulating cell proliferation, apoptosis, migration, antioxidative stress. Its potential significance warrants further investigation, given altered adaptable metabolism tumor cells. It has been reported that both high low levels expression are associated diseases, arthritis, cancer, diabetes, brain infections, well worse prognoses. attributed to oncogenic tumor-suppressive features. concluded acts foe responds metabolic cellular stress signals promote survival against apoptosis. Conversely, normal friend safeguard oxidative Therefore, could serve viable biomarker or even pharmacological target.
Language: Английский
Citations
5
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: July 5, 2024
Abstract Background Accompanied by activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, aberrant connexin 43 (Cx43) hemichannel-mediated ATP release is situated upstream inflammasome assembly and inflammation contributes to multiple secondary complications diabetes associated cardiometabolic comorbidities. Evidence suggests there may be a link between Cx43 hemichannel activity in diabetic kidney. The consequences blocking tubular priming/activation NLRP3 model kidney disease (DKD) was investigated. We examined downstream markers proinflammatory chemoattractant role secretome on macrophage recruitment activation. Methods Analysis human transcriptomic data from Nephroseq repository correlated gene expression renal function DKD. Primary proximal tubule epithelial cells (RPTECs) monocyte-derived macrophages (MDMs) were cultured high glucose inflammatory cytokines as DKD assess activity, epithelial-to-macrophage paracrine-mediated crosstalk. Tonabersat assessed for hemichannels. Results Transcriptomic analysis biopsies patients with showed that increased declining glomerular filtration rate (GFR) proteinuria. In vitro, blocked glucose/cytokine-dependant increases reduced RPTECs. observed reciprocal relationship which exacerbated release, events driven nuclear factor kappa-B (NFκB)-mediated priming opening, changes Tonabersat. Conditioned media (CM) RPTECs treated glucose/cytokines MDMs, an effect when pre-treated Co-culture using conditioned Tonabersat-treated dampened marker migration. Conclusion Using DKD, we report first time trigger instigate NLRP3-induced Recapitulating observations previously reported retinopathy, these suggest blockers (i.e., Tonabersat) dampen multi-system damage diabetes.
Language: Английский
Citations
4
Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117842 - 117842
Published: Jan. 13, 2025
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: Feb. 19, 2025
Chronic inflammation and immune imbalance mediated by macrophages are considered pivotal in diabetic kidney disease (DKD). The study aims to clarify the macrophage heterogeneity phenotype dynamics, pinpoint critical targets within efferocytosis DKD. Utilizing early human DKD sequencing data, we computed potential communication between leukocytes renal intrinsic cells. Subsequently, scrutinized single-cell RNA (scRNA-seq) data from CD45-enriched cells, concentrating on subsets Pseudotime trajectory analysis was conducted explore cell development. Differential expression genes (DEGs) subgroups bulk RNA-sequencing were used identify shared hub genes. NephroseqV5 platform employed evaluate clinical significance, of key molecules validated tissues. Macrophage infiltration rose DKD, causing through release chemokines. As time progressed, number resident substantially dropped, with diminishing M1-like increasing M2-like phenotypes relative stages. Further pointed most enrichment function is phagosome. We overlapped DEGs efferocytosis-related identified genes, including CD36, ITGAM, CX3CR1, which exhibited significant correlations T Nephroseq database revealed that they associated proteinuria function. Consistent validation set, vivo experiments verified elevated levels molecules. In essence, our research elucidated dynamics subtype transitions. It emphasized three as modulators indicating their innovative biomarkers therapeutic targets.
Language: Английский
Citations
0