Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

Shi, Yingfeng; Hu, Yan; Cui, Binbin; Zhuang, Songlin; Liu, Na

doi:10.1177/08968608211004683

Cited by 13 publications

(18 citation statements)

References 157 publications

(228 reference statements)

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“…Among all molecules that regulate peritoneal angiogenesis, VEGF as a strong pro-angiogenic factor binds to VEGFR expressed on the cell surface of vascular endothelial cells, stimulating the formation of new capillaries in the peritoneal membrane. Increased effective vascular surface area accelerates glucose uptake from the dialysate into the circulation, leading to a dissipation of glucose-driven osmotic pressure, which ultimately results in ultrafiltration failure (UF) (Aroeira et al, 2005;Saxena, 2008;de Lima et al, 2013;Shi et al, 2022). The selective high expression of endoglin on tumour vessels has led to widespread attention to it as a target for cancer therapy, reminding us whether anti-endoglin treatment could similarly improve peritoneal angiogenesis and thus reduce PF (Paauwe et al, 2016;Kasprzak and Adamek, 2018;Liu et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Endoglin aggravates peritoneal fibrosis by regulating the activation of TGF-β/ALK/Smads signaling

Huang

Xiao²,

Lü³

et al. 2022

Front. Pharmacol.

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Background: Peritoneal fibrosis (PF) is an intractable complication in patients on long-term peritoneal dialysis (PD). Transforming growth factor-β (TGF-β) is a key pro-fibrogenic factor involved in PD-associated PF, and endoglin, as a coreceptor for TGF-β, plays a role in balancing the TGF-β signaling pathway. Here, we investigated whether endoglin could be a potential therapeutic target for PF.Methods:In vivo, we established PF model in SD rats by daily intraperitoneal injection of peritoneal dialysis fluids (PDF) containing 4.25% glucose for 6 weeks and downregulated endoglin expression by tail vein injection of AAV9-ENG on day 14 to assess the effect of endoglin on peritoneal morphology and markers related to fibrosis, angiogenesis, and epithelial-mesenchymal transition (EMT). In vitro, we treated human peritoneal mesothelial cells (HPMCs) transfected with ENG siRNA in high glucose medium to explore the potential mechanism of endoglin in PF.Results: Compared to control group, continuous exposure to biologically incompatible PDF induced exacerbated PF, accompanied by a significant increase in endoglin expression. Conversely, knockdown of endoglin ameliorated peritoneal injury characterized by increased peritoneal thickening and collagen deposition, angiogenesis, as well as EMT. Consistently, HPMCs cultured in high glucose medium underwent the EMT process and exhibited over-expression of fibronectin, collagen type I, vascular endothelial growth factor (VEGF), whereas these aforementioned alterations were alleviated after ENG siRNA transfection. In addition, we also found that ENG siRNA inhibited TGF-β-induced phosphorylation of Smad2/3 and Smad1/5/9 in HPMCs treated with high glucose (HG).Conclusion: Our findings confirmed for the first time that endoglin exacerbated PF by regulating the activation of TGF-β/ALK/Smads signaling, which will provide a novel potential therapeutic target in PF.

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Section: Discussionmentioning

confidence: 99%

Endoglin aggravates peritoneal fibrosis by regulating the activation of TGF-β/ALK/Smads signaling

Huang

Xiao²,

Lü³

et al. 2022

Front. Pharmacol.

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“…Indeed, the density of peritoneal microvessels predicts glucose transport independent of other factors (25). On the molecular level, VEGF is the best characterized mediator of angiogenesis (28) and it plays a role in peritoneal membrane dysfunction in PD (17,29,30). Prior studies identified the mesothelium as an important source of VEGF in the peritoneum and deciphered pathways of VEGF induction during PD (16,17,(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy

et al. 2022

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Peritoneal dialysis (PD) is a valuable ‘home treatment’ option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy.

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“…Moreover, a review newly published by our team systematically summarizes the angiogenic effect of VEGF. VEGF is associated with high peritoneal transport rate while impaired mesothelial cells are the major sources of VEGF in the peritoneum 30 …”

Section: Introductionmentioning

confidence: 99%

“…VEGF is associated with high peritoneal transport rate while impaired mesothelial cells are the major sources of VEGF in the peritoneum. 30 Since the evaluation of peritoneal function of patients is after the start of peritoneal dialysis, there are still a large number of patients with initial high PSTR who undergo PD and their prognosis is not clear. This study was undertaken to evaluate the subsequent overall survival and technique survival of the PD patients grouped by their baseline peritoneal transport status, analyse independent predictive risk factors of high baseline peritoneal transport status and explore its potential pathogenesis through in vitro experiments.…”

Section: Introductionmentioning

confidence: 99%

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The prognosis and risk factors of baseline high peritoneal transporters on patients with peritoneal dialysis

Huang

Wang

Shi

et al. 2021

J Cellular Molecular Medi

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The relationship between baseline high peritoneal solute transport rate (PSTR) and the prognosis of peritoneal dialysis (PD) patients remains unclear. The present study combined clinical data and basic experiments to investigate the impact of baseline PSTR and the underlying molecular mechanisms. A total of 204 incident CAPD patients from four PD centres in Shanghai between 1 January 2014 and 30 September 2020 were grouped based on a peritoneal equilibration test after the first month of dialysis. Analysed with multivariate Cox and logistic regression models, baseline high PSTR was a significant risk factor for technique failure (AHR 5.70; 95% CI 1.581 to 20.548 p = 0.008). Baseline hyperuricemia was an independent predictor of mortality (AHR 1.006 95%CI 1.003 to 1.008, p < 0.001) and baseline high PSTR (AOR 1.007; 95%CI 1.003 to 1.012; p = 0.020). Since uric acid was closely related to high PSTR and adverse prognosis, the in vitro experiments were performed to explore the underlying mechanisms of which uric acid affected peritoneum. We found hyperuricemia induced epithelial‐to‐mesenchymal transition (EMT) of cultured human peritoneal mesothelial cells by activating TGF‐β1/Smad3 signalling pathway and nuclear transcription factors. Conclusively, high baseline PSTR induced by hyperuricaemia through EMT was an important reason of poor outcomes in CAPD patients.

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Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

Cited by 13 publications

References 157 publications

Endoglin aggravates peritoneal fibrosis by regulating the activation of TGF-β/ALK/Smads signaling

Endoglin aggravates peritoneal fibrosis by regulating the activation of TGF-β/ALK/Smads signaling

Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy

The prognosis and risk factors of baseline high peritoneal transporters on patients with peritoneal dialysis

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