Role of Src in Vascular Hyperpermeability Induced by Advanced Glycation End Products

Zhang, Wei-Jin; Xu, Qiong; Wu, Jie; Zhou, Xiaoyan; Weng, Jie; Xu, Jing; Wang, Weiju; Huang, Qiaobing; Guo, Xiaohua

doi:10.1038/srep14090

Cited by 43 publications

(55 citation statements)

References 50 publications

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“…We have revealed a significant exudation of FITC-dextran from mesenteric venules in AGE-treated wild type mice. However, this exudation was markedly reduced in RAGE knockout mice, which further confirmed the role of RAGE in vascular hyperpermeability in vivo [35]. Moreover, we have shown that LPS caused significant rearrangement of cytoskeletal filament F-actin in insolated wild-type mouse pulmonary microvascular endothelial cells (PMVECs).…”

Section: Discussionsupporting

confidence: 63%

RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability

Wang

Guo

et al. 2017

Sensors

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Endothelial functional dysregulation and barrier disruption contribute to the initiation and development of sepsis. The receptor for advanced glycation end products (RAGE) has been demonstrated to be involved in the pathogenesis of sepsis. The present study aimed to investigate the role of RAGE in lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation in endothelial cells and the consequent endothelial hyperpermeability. LPS-induced upregulation of RAGE protein expression in human umbilical vein endothelial cells (HUVECs) was detected by western blotting. Activation of NF-κB was revealed using western blotting and immunofluorescent staining. LPS-elicited endothelial hyperpermeability was explored by transendothelial electrical resistance (TER) assay and endothelial monolayer permeability assay. The blocking antibody specific to RAGE was used to confirm the role of RAGE in LPS-mediated NF-κB activation and endothelial barrier disruption. We found that LPS upregulated the protein expression of RAGE in a dose- and time-dependent manner in HUVECs. Moreover, LPS triggered a significant phosphorylation and degradation of IκBα, as well as NF-κB p65 nuclear translocation. Moreover, we observed a significant increase in endothelial permeability after LPS treatment. However, the RAGE blocking antibody attenuated LPS-evoked NF-κB activation and endothelial hyperpermeability. Our results suggest that RAGE plays an important role in LPS-induced NF-κB activation and endothelial barrier dysfunction.

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Section: Discussionsupporting

confidence: 63%

RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability

Wang

Guo

et al. 2017

Sensors

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“…Previously, we have shown that Src acts like a signal node and elicits an endothelial permeability increase upon AGE stimulation, whereas both the inhibition of AGEs binding to RAGE and the downregulation of Src significantly ameliorated AGE‐induced F‐actin rearrangement and hyperpermeability. Consistently, Src upregulation with the dominant active mutant, Src K298M, duplicated the barrier disruptive effect . The main underlying mechanism involved has been investigated in our laboratory.…”

Section: Mechanism Of Age‐induced Endothelial Dysfunctionmentioning

confidence: 68%

Role of moesin, Src, and ROS in advanced glycation end product‐induced vascular endothelial dysfunction

Zhang

Guo

et al. 2017

Microcirculation

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The disruption of endothelial integrity and the occurrence of angiogenesis in response to AGEs contribute greatly to micro- and macrovascular complications associated with DM. Among human dermal, brain, and retinal vascular ECs, activation of ERM, moesin, by phosphorylation of Thr-558 is involved in AGE-induced hyperpermeability and angiogenesis via the Rho and ROCK (Rho/ROCK) and p38 pathways. Src also plays an important role in AGE-induced endothelial barrier dysfunction by phosphorylating moesin, VE-cadherin, and FAK. Furthermore, recent studies have demonstrated that ROS serve as a key mediator of the AGE-induced endothelial response. ROS inhibition would greatly benefit ECs. This review focuses on the role of moesin in microvascular permeability and angiogenesis, and on the involvement of Src and ROS in endothelial barrier disruption.

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“…First of all, smoking has chronic effects, by diminishing nitric oxide availability and endothelial celldependent vasodilation, which lead to an enhanced oxidative stress, glomerulosclerosis and tubular atrophy [53,54]. Moreover, cigarette smoke contains glycotoxins which induce advance glycation end products (AGEPs) and thus directly promote pathological vascular changes [55]. On the other hand, evidence of a link between smoking habit and Doppler-RI impairment are limited.…”

Section: Plos Onementioning

confidence: 99%

Renal resistive index in chronic kidney disease patients: Possible determinants and risk profile

et al. 2020

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BackgroundHigh ultrasound renal resistive index (RI) predicts poor cardiorenal outcomes in chronic kidney disease (CKD) and has recently emerged as a marker of nephroprotective drugs response. Thus, having a risk profile of CKD patients with abnormal RI may be relevant for the clinicians. MethodsConsecutive patients referred to our non-dialysis CKD clinic from 01/01/2016 to 01/12/2016, were evaluated by clinical and ultrasound analysis. Inclusion criteria were age >18 years and presence of CKD defined as estimated glomerular filtration rate (eGFR)<60 mL/min/ 1.73m 2 and/or proteinuria>0.150g/24h. Renal artery stenosis, solitary kidney, acute kidney injury were the main exclusion criteria. RI value was the mean of three measures in segmental arteries in each kidney. Univariate analysis was performed to evaluate associations between continuous RI and clinical variables. Multivariate linear regression analysis, based on stepwise method with an elimination criterion of p<0.10, was used to assess the independent correlates of RI as continuous variable. ResultsWe studied 73 patients (69.9% men). Mean RI was 0.67±0.09. Frequencies of diabetes and cardiovascular disease (CVD) were 19.2% and 20.6% and median eGFR 54.1 [30.0-84.6] mL/min/1.73m 2 . From low (<0.65) to intermediate (0.65-0.70) to high (>0.70) RI categories, eGFR and haemoglobin levels were decreased while diabetes, cardiovascular disease (CVD), phosphate and smokers were higher. At univariate analysis, RI was significantly associated with age, presence of diabetes, CVD, serum phosphorus, eGFR, Urea and haemoglobin. Multi-adjusted stepwise regression analysis showed that lower eGFR levels PLOS ONE

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Role of Src in Vascular Hyperpermeability Induced by Advanced Glycation End Products

Cited by 43 publications

References 50 publications

RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability

RAGE Plays a Role in LPS-Induced NF-κB Activation and Endothelial Hyperpermeability

Role of moesin, Src, and ROS in advanced glycation end product‐induced vascular endothelial dysfunction

Renal resistive index in chronic kidney disease patients: Possible determinants and risk profile

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