Pathophysiological Mechanisms of Peritoneal Fibrosis and Peritoneal Membrane Dysfunction in Peritoneal Dialysis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8607 - 8607

Published: Aug. 7, 2024

The characteristic feature of chronic peritoneal damage in dialysis (PD) is a decline ultrafiltration capacity associated with pathological fibrosis and angiogenesis. pathogenesis attributed to bioincompatible factors PD fluid peritonitis. Uremia membrane inflammation that affects fibrosis, neoangiogenesis, baseline function. Net volume affected by capillary surface area, vasculopathy, lymphangiogenesis. Many inflammatory cytokines induce fibrogenic growth factors, crosstalk between macrophages fibroblasts. Transforming factor (TGF)-β vascular endothelial (VEGF)-A are the key mediators angiogenesis, respectively. Bioincompatible upregulate TGF-β expression mesothelial cells contributes development fibrosis. Angiogenesis lymphangiogenesis can progress during via TGF-β–VEGF-A/C pathways. Complement activation occurs fungal peritonitis progresses insidiously PD. Analyses human have clarified mechanisms which encapsulating sclerosis develops. Different effects dialysates on were also recognized, particularly terms damage. Understanding pathophysiologies will lead preservation function improvements technical survival, mortality, quality life for patients.

Language: Английский

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The role of macrophage-derived Exosomes in reversing peritoneal fibrosis: Insights from Astragaloside IV

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155683 - 155683

Published: April 25, 2024

Language: Английский

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Relationship between glucose to lymphocyte ratio and the first peritonitis episode in patients treated with peritoneal dialysis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 26, 2025

This study aimed to investigate the potential relationship between baseline glucose lymphocyte ratio (GLR) levels and first episode of peritonitis in patients treated with peritoneal dialysis (PD). A total 314 PD were included divided into three groups based on GLR tertiles: tertile 1 (GLR ≤ 4.23); 2 (4.23 < 5.96), 3 > 5.96). The relationships analyzed using Kaplan–Meier curves multivariable Cox regression models. Competitive risk analysis, subgroup sensitivity analyses performed validate robustness findings. During a median follow-up 27 months, 123 (39.17%) developed peritonitis. incidence increased higher tertiles (tertile 1: 32.08%, 2: 37.50%, 3: 48.08%). revealed significant differences cumulative among (Log-Rank test, P = 0.018). After full adjustment for confounding factors, remained at significantly compared those (HR 2.633, 95% CI 1.223–5.668, 0.013). models analysis further confirmed this association. Our suggests that elevated is associated an PD.

Language: Английский

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Shenbing Decoction III and Apigenin Improve Peritoneal Fibrosis Mediated by Epithelial–Mesenchymal Transition Through TAK1/p38MAPK/NF‐κB Pathways

Journal of Food Biochemistry, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: This study aimed to evaluate the effect of Shenbing Decoction III (SBD III) and its key Apigenin on peritoneal dialysis (PD)–induced fibrosis explore underlying mechanisms. Methods: Liquid chromatography–mass spectrometry confirmed presence in SBD III. Human mesothelial cells (HMrSV5) were stimulated with PD solution (PDS) induce fibrosis, treatment was administered. Results: PDS decreased cell viability increased migration invasion capabilities HMrSV5 cells. It also reduced E‐cadherin expression, while increasing expression α‐SMA, fibronectin, collagen I, TGF‐β1. effectively counteracted these effects. Additionally, inhibited PDS‐induced upregulation phosphorylation transforming growth factor‐β‐activated kinase 1 (TAK1), p38, nuclear factor‐κB (NF‐κB), similar effects 5z‐7‐oxozeaenol. Chronic kidney disease (CKD) induced mice by 5/6 nephrectomy, followed treatment. The therapeutic evaluated. CKD exhibited body weight indices, along elevated blood urea nitrogen, urinary creatinine, protein levels. Fibrosis observed kidneys peritoneum. significantly alleviated Notably, further augmented when Conclusion: ameliorated inhibiting epithelial–mesenchymal transition via TAK1/p38MAPK/NF‐κB pathway, indicating promising pharmaceutical candidates for CKD.

Language: Английский

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Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: April 22, 2025

Acute kidney injury (AKI) substantially increases the risk of developing and worsening chronic disease (CKD). The shift from AKI to CKD is a complex process that involves various cell types, with macrophages playing key role in responding renal injury. M1 M2 macrophages-the two main types macrophages-have distinct functions at stages. induce damage by secreting pro-inflammatory cytokines immediately after injury, whereas subsequently facilitate tissue repair. conversion subtype vital for effective repair However, when infiltrate persistently, they can paradoxically cause fibrosis, thereby complicating recovery. As epigenetic regulatory factor, deacetylase SIRT6 exerts biological effects through its enzymatic reactions, including regulation cellular metabolism, antioxidant stress response, inhibition fibrosis. expressed all major resident cells demonstrated protect kidneys. promotes transition subtype; nevertheless, this poses fibrosis if remain because influence SIRT6. This review aimed (i) delve into intricate macrophage polarization toward context progression (ii) explore potential strategies may effectively target mitigate CKD.

Language: Английский

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Tamoxifen exerts anti-peritoneal fibrosis effects by inhibiting H19-activated VEGFA transcription

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 11, 2023

Abstract Background Peritoneal dialysis (PD) remains limited due to failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported treat fibrosis, but the underlying mechanism unknown. In this study, we sought explore whether tamoxifen played anti-fibrotic role affecting transcription factor ESR1. Methods ESR1 expression was detected in human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40 mM methylglyoxal for 2 weeks establish PD-induced administrated gavage, at dose 10 mg/kg. Chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assay performed validate bound H19 promoter. Gain-of-function loss-of-function experiments investigate biological roles on mesothelial-mesenchymal transition (MMT) mesothelial cells (HPMCs). Intraperitoneal injection nanomaterial-wrapped 2′- O -Me-modified small interfering RNA applied suppress mouse pull-down assays demonstrated binding between p300. Exfoliated obtained from effluent analyze correlations (or H19) solute transfer rate (PSTR). Results increased significantly peritoneum after long-term exposure dialysate. treatment ameliorated high glucose-induced MMT HPMCs, improved ultrafiltration rate, decreased PSTR reduced level decreasing . Depletion reversed pro-fibrotic effect while ectopic exacerbated fibrotic pathological changes. siRNAs targeting mitigated PD-related fibrosis mice. (RIP) results delineated that activated VEGFA p300 promoter inducing histone acetylation promising targets predict function. Conclusions High via activating cells, transcribed binds cofactor activate Targeting ESR1/H19/VEGFA pathway provided new hope patients undergoing dialysis. Graphic

Language: Английский

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Mechanisms of mesothelial cell response to viral infections: HDAC1-3 inhibition blocks poly(I:C)-induced type I interferon response and modulates the mesenchymal/inflammatory phenotype

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 27, 2024

Infectious peritonitis is a leading cause of peritoneal functional impairment and primary factor for therapy discontinuation in dialysis (PD) patients. Although bacterial infections are common episodes, emerging evidence suggests role viral pathogens. Toll-like receptors (TLRs) specifically recognize conserved pathogen-associated molecular patterns (PAMPs) from bacteria, viruses, fungi, thereby orchestrating the ensuing inflammatory/immune responses. Among TLRs, TLR3 recognizes dsRNA triggers antiviral response cascades upon activation. Epigenetic regulation, mediated by histone deacetylase (HDAC), has been demonstrated to control several cellular functions various extracellular stimuli. Employing epigenetic target modulators, such as epidrugs, current therapeutic option cancers holds promise treating diseases. This study aims elucidate impact stimulation on plasticity human mesothelial cells (MCs) PD patients investigate effects HDAC1-3 inhibition. Treatment MCs with agonist polyinosinic:polycytidylic acid (Poly(I:C)), led acquisition bona fide mesothelial-to-mesenchymal transition (MMT) characterized upregulation mesenchymal genes loss epithelial-like features. Moreover, Poly(I:C) modulated expression inflammatory cytokines chemokines. A quantitative proteomic analysis treated MS-275, an inhibitor, unveiled altered proteins, including cytokines/chemokines interferon-stimulated (ISGs). MS-275 facilitated MMT reversal inhibited interferon signature, which was associated reduced STAT1 phosphorylation. However, modulation cytokine/chemokine production not univocal, IL-6 CXCL8 were augmented while TNF-α CXCL10 decreased. Collectively, our findings underline significance acquiring mesenchymal-like phenotype potential consequences virus-associated episodes The observed promotion inhibition albeit without general cytokine production, translational implications deserving further analysis.

Language: Английский

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Pressure induces peritoneal fibrosis and inflammation through CD44 signaling

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: July 31, 2024

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact pressure on peritoneum remains unclear. In present study, we hypothesized increased potential contributing factor to fibrosis investigated possible mechanisms. vitro experiments found that pressurization led mesenchymal phenotype, expression fibrotic markers inflammatory factors in human mesothelial MeT-5A cells. Pressure also cell proliferation augmented migration The mouse model equilibrium test (PET) data both showed positive association between higher small solute transport, along decreased net UF. Mechanistically, significant upregulation CD44 cells upon pressurization. Notably, treatment neutralizing antibodies prevented pressure-induced phenotypic changes cells, while inhibitor oligo-fucoidan ameliorated thickening, inflammation mice. To conclude, intraperitoneal results via CD44-mediated inflammation. blockage can be utilized as novel preventive approach for PD-related UF

Language: Английский

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HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Dec. 13, 2023

Background Despite the significant progress achieved in understanding pathology and clinical management of SARS-CoV-2 infection, still pathogenic issues need to be clarified. Treatment with modulators epigenetic targets, i.e., epidrugs, is a current therapeutic option several cancers could represent an approach therapy viral diseases. Results Aim this study was analysis role histone deacetylase (HDAC) inhibition modulation infection mesothelial cells (MCs). MeT5A cells, pleura MC line, were pre-treated different specific class I IIb HDAC inhibitors. Unexpectedly, treatment HDAC1-3 inhibitors significantly increased ACE2/TMPRSS2 expression, suggesting favoring infection. We focused our on most potent inducer among analysed, MS-275, inhibitor. expression validated by Western Blot (WB) immunofluorescence. The involvement receptor induction confirmed HDAC1/HDAC2 silencing. In accordance data, MS-275 replication virus propagation Vero E6 cells. Notably, able increase production, although lesser extent, also lung adenocarcinoma cell line Calu-3 Mechanistically, H3 H4 acetylation at promoters, increasing their transcription. Conclusion This highlights previously unrecognized effect entry, productive correlating ACE2 TMPRSS2. These while adding basic insight into COVID-19 pathogenesis, warn for use patients.

Language: Английский

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Intercellular communication in peritoneal dialysis

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

Published: Feb. 8, 2024

Long-term peritoneal dialysis (PD) causes structural and functional alterations of the membrane. Peritoneal deterioration fibrosis are multicellular multimolecular processes. Under stimulation by deleterious factors such as non-biocompatibility PD solution, various cells in abdominal cavity show differing characteristics, secretion different cytokines, varying protein expression levels, transdifferentiation into other cells. In this review, we discuss role their interactions pathogenesis PD. An in-depth understanding intercellular communication inter-organ will lead to a better disease, enabling development novel therapeutic targets.

Language: Английский

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