文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

白细胞介素-6 通过转信号通路下调血管内皮钙黏蛋白表达并增加肾小球内皮细胞通透性。

Interleukin-6 Downregulates the Expression of Vascular Endothelial-Cadherin and Increases Permeability in Renal Glomerular Endothelial Cells via the Trans-Signaling Pathway.

机构信息

Department of Pediatrics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning province, China.

Department of Pediatrics, Tangshan Maternal and Child Health Hospital, Tangshan, 063000, Hebei province, China.

出版信息

Inflammation. 2022 Dec;45(6):2544-2558. doi: 10.1007/s10753-022-01711-3. Epub 2022 Jul 23.

DOI:10.1007/s10753-022-01711-3
PMID:35870042
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9646551/
Abstract

The pathogenesis of IgA nephropathy (IgAN) is still unknown, but reportedly, interleukin 6 (IL-6) is involved in this process. However, its role in damaging glomerular endothelial cells is still unclear. Therefore, in this study, to clarify the mechanism of the pathogenesis of IgAN, we investigated the effect of IL-6 on the permeability of glomerular endothelial cells. A rat model of IgAN was established, and the animals divided into two groups, namely, the normal and IgAN groups. Glomerular endothelial cell injury was evaluated via electron microscopy. Furthermore, IL-6-induced changes in the permeability of human renal glomerular endothelial cells (HRGECs) were measured via trans-endothelial resistance (TEER) measurements and fluorescein isothiocyanate-dextran fluorescence. Furthermore, vascular endothelial-cadherin (VE-cadherin) was overexpressed to clarify the effect of IL-6 on HRGEC permeability, and to determine the pathway by which it acts. The classical signaling pathway was blocked by silencing IL-6R and the trans-signaling pathway was blocked by sgp30Fc. In IgAN rats, electron microscopy showed glomerular endothelial cell damage and western blotting revealed a significant increase in IL-6 expression, while VE-cadherin expression decreased significantly in the renal tissues. IL-6/IL-6R stimulation also significantly increased the permeability of HRGECs (p < 0.05). This effect was significantly reduced by VE-cadherin overexpression (p < 0.01). After IL-6R was silenced, IL-6/IL-6R still significantly reduced VE-cadherin expression and sgp30Fc blocked the trans-signaling pathway as well as the upregulation of IL-6/IL-6R-induced VE-cadherin expression. This suggests that IL-6 mainly acts via the trans-signaling pathway. IL-6 increased the permeability of HRGECs by decreasing the expression of VE-cadherin via the trans-signaling pathway.

摘要

IgA 肾病（IgAN）的发病机制尚不清楚，但据报道白细胞介素 6（IL-6）参与了这一过程。然而，其在损伤肾小球内皮细胞中的作用尚不清楚。因此，在这项研究中，为了阐明 IgAN 发病机制，我们研究了 IL-6 对肾小球内皮细胞通透性的影响。建立了 IgAN 大鼠模型，将动物分为正常组和 IgAN 组。通过电子显微镜评估肾小球内皮细胞损伤。此外，通过跨内皮电阻（TEER）测量和荧光素异硫氰酸酯-葡聚糖荧光测量来测量 IL-6 诱导的人肾肾小球内皮细胞（HRGEC）通透性变化。此外，过表达血管内皮钙黏蛋白（VE-cadherin）以阐明 IL-6 对 HRGEC 通透性的影响，并确定其作用途径。通过沉默 IL-6R 阻断经典信号通路，通过 sgp30Fc 阻断转信号通路。在 IgAN 大鼠中，电子显微镜显示肾小球内皮细胞损伤，Western blot 显示 IL-6 表达显著增加，而肾脏组织中 VE-cadherin 表达显著降低。IL-6/IL-6R 刺激也显著增加了 HRGEC 的通透性（p<0.05）。过表达 VE-cadherin 可显著降低这种作用（p<0.01）。沉默 IL-6R 后，IL-6/IL-6R 仍显著降低 VE-cadherin 表达，sgp30Fc 阻断转信号通路以及 IL-6/IL-6R 诱导的 VE-cadherin 表达上调。这表明 IL-6 主要通过转信号通路起作用。IL-6 通过转信号通路降低 VE-cadherin 的表达，增加 HRGEC 的通透性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/e615126ec2aa/10753_2022_1711_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/7f150b0bb8f3/10753_2022_1711_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/9fbfd3c6bd4e/10753_2022_1711_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/5573632ade84/10753_2022_1711_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/634d1e30f8fb/10753_2022_1711_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/9d026a4060c1/10753_2022_1711_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/e615126ec2aa/10753_2022_1711_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/7f150b0bb8f3/10753_2022_1711_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/9fbfd3c6bd4e/10753_2022_1711_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/5573632ade84/10753_2022_1711_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/634d1e30f8fb/10753_2022_1711_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/9d026a4060c1/10753_2022_1711_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb5/9646551/e615126ec2aa/10753_2022_1711_Fig6_HTML.jpg

相似文献

[1]
Interleukin-6 Downregulates the Expression of Vascular Endothelial-Cadherin and Increases Permeability in Renal Glomerular Endothelial Cells via the Trans-Signaling Pathway.

Inflammation. 2022-12

[2]
Interleukin-1β increases permeability and upregulates the expression of vascular endothelial-cadherin in human renal glomerular endothelial cells.

Mol Med Rep. 2015-5

[3]
Low-Dose X-Ray Increases Paracellular Permeability of Human Renal Glomerular Endothelial Cells.

Comput Math Methods Med. 2022

[4]
Sinomenine alleviates glomerular endothelial permeability by activating the C/EBP-α/claudin-5 signaling pathway.

Hum Cell. 2022-9

[5]
Erythropoietin maintains VE-cadherin expression and barrier function in experimental diabetic retinopathy via inhibiting VEGF/VEGFR2/Src signaling pathway.

Life Sci. 2020-8-12

[6]
[Paeoniflorin improves the permeability of cardiac microvascular endothelial cells by regulating Src/vascular endothelial-cadherin pathway].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020-1

[7]
Human mesenchymal stem cells inhibit vascular permeability by modulating vascular endothelial cadherin/β-catenin signaling.

Stem Cells Dev. 2010-10-18

[8]
Sitagliptin protects renal glomerular endothelial cells against high glucose-induced dysfunction and injury.

Bioengineered. 2022-1

[9]
HIF-1α Enhances Vascular Endothelial Cell Permeability Through Degradation and Translocation of Vascular Endothelial Cadherin and Claudin-5 in Rats With Burn Injury.

J Burn Care Res. 2021-3-4

[10]
Orai-vascular endothelial-cadherin signaling complex regulates high-glucose exposure-induced increased permeability of mouse aortic endothelial cells.

BMJ Open Diabetes Res Care. 2021-4

引用本文的文献

[1]
Protective Effects of Luteolin on -Induced Injury: An In Vitro Study with Porcine Vascular Endothelial Cells.

Antibiotics (Basel). 2025-8-12

[2]
Inflammation-associated molecules in the glomerular-endothelium in mild IgA-nephropathy patients identified by single-cell and spatial transcriptome.

Commun Biol. 2025-6-12

[3]
Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease.

Am J Physiol Renal Physiol. 2025-7-1

[4]
ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.

Commun Biol. 2025-3-15

[5]
Single-Cell Analysis of Endothelial Cell Injury in IgA Nephropathy.

Immun Inflamm Dis. 2025-2

[6]
IL-6 and diabetic kidney disease.

Front Immunol. 2024-12-19

[7]
Loss of filamentous actin, tight junction protein expression, and paracellular barrier integrity in frataxin-deficient human brain microvascular endothelial cells-implications for blood-brain barrier physiology in Friedreich's ataxia.

Front Mol Biosci. 2024-1-11

[8]
Endothelial Cell Dysfunction and Increased Cardiovascular Risk in Patients With Chronic Kidney Disease.

Circ Res. 2023-4-14

[9]
Molecular insight in intrarenal inflammation affecting four main types of cells in nephrons in IgA nephropathy.

Front Med (Lausanne). 2023-3-9

本文引用的文献

[1]
Blocking only the bad side of IL-6 in inflammation and cancer.

Cytokine. 2021-12

[2]
hnRNPA2/B1 Ameliorates LPS-Induced Endothelial Injury through NF-B Pathway and VE-Cadherin/-Catenin Signaling Modulation In Vitro.

Mediators Inflamm. 2020

[3]
Naringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathway.

Biosci Rep. 2020-3-27

[4]
Increased Non-switched Memory B Cells are Associated with Plasmablasts, Serum IL-6 Levels and Renal Functional Impairments in IgAN Patients.

Immunol Invest. 2019-10-31

[5]
Response to IL-6 trans- and IL-6 classic signalling is determined by the ratio of the IL-6 receptor α to gp130 expression: fusing experimental insights and dynamic modelling.

Cell Commun Signal. 2019-5-17

[6]
Vascular endothelial cadherin shedding is more severe in sepsis patients with severe acute kidney injury.

Crit Care. 2019-1-18

[7]
Soluble gp130 prevents interleukin-6 and interleukin-11 cluster signaling but not intracellular autocrine responses.

Sci Signal. 2018-10-2

[8]
Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells.

Exp Eye Res. 2018-9-18

[9]
Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells.

Cell Commun Signal. 2018-9-5

[10]
Standardized classification and reporting of glomerulonephritis.

Nephrol Dial Transplant. 2019-2-1

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索