scholarly journals Histidine‐rich glycoprotein ameliorates endothelial barrier dysfunction through regulation of NF‐κB and MAPK signal pathway

2019 ◽  
Vol 176 (15) ◽  
pp. 2808-2824 ◽  
Author(s):  
Shangze Gao ◽  
Hidenori Wake ◽  
Yuan Gao ◽  
Dengli Wang ◽  
Shuji Mori ◽  
...  
Keyword(s):  
Signal Pathway ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Mapk Signal Pathway

scholarly journals SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Hao Shen ◽  
Jr-Yu Lin ◽  
Cheng-Yo Lu ◽  
Sung-Sen Yang ◽  
Chung-Kan Peng ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Knockout Mice ◽  
Barrier Function ◽  
Alveolar Epithelium ◽  
Signal Pathway ◽  
Control Group ◽  
Barrier Dysfunction ◽  
Hyperoxic Exposure ◽  
Monolayer Permeability ◽  
Mapk Signal Pathway

Abstract Background Hyperoxia downregulates the tight junction (TJ) proteins of the alveolar epithelium and leads to barrier dysfunction. Previous study has showed that STE20/SPS1-related proline/alanine-rich kinase (SPAK) interferes with the intestinal barrier function in mice. The aim of the present study is to explore the association between SPAK and barrier function in the alveolar epithelium after hyperoxic exposure. Methods Hyperoxic acute lung injury (HALI) was induced by exposing mice to > 99% oxygen for 64 h. The mice were randomly allotted into four groups comprising two control groups and two hyperoxic groups with and without SPAK knockout. Mouse alveolar MLE-12 cells were cultured in control and hyperoxic conditions with or without SPAK knockdown. Transepithelial electric resistance and transwell monolayer permeability were measured for each group. In-cell western assay was used to screen the possible mechanism of p-SPAK being induced by hyperoxia. Results Compared with the control group, SPAK knockout mice had a lower protein level in the bronchoalveolar lavage fluid in HALI, which was correlated with a lower extent of TJ disruption according to transmission electron microscopy. Hyperoxia down-regulated claudin-18 in the alveolar epithelium, which was alleviated in SPAK knockout mice. In MLE-12 cells, hyperoxia up-regulated phosphorylated-SPAK by reactive oxygen species (ROS), which was inhibited by indomethacin. Compared with the control group, SPAK knockdown MLE-12 cells had higher transepithelial electrical resistance and lower transwell monolayer permeability after hyperoxic exposure. The expression of claudin-18 was suppressed by hyperoxia, and down-regulation of SPAK restored the expression of claudin-18. The process of SPAK suppressing the expression of claudin-18 and impairing the barrier function was mediated by p38 mitogen-activated protein kinase (MAPK). Conclusions Hyperoxia up-regulates the SPAK-p38 MAPK signal pathway by ROS, which disrupts the TJ of the alveolar epithelium by suppressing the expression of claudin-18. The down-regulation of SPAK attenuates this process and protects the alveolar epithelium against the barrier dysfunction induced by hyperoxia.

scholarly journals Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo

2008 ◽  
Vol 74 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Robert Fürst ◽  
Martin F. Bubik ◽  
Peter Bihari ◽  
Bettina A. Mayer ◽  
Alexander G. Khandoga ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Atrial Natriuretic

scholarly journals Microtubule destabilization caused by particulate matter contributes to lung endothelial barrier dysfunction and inflammation

2019 ◽  
Vol 53 ◽  
pp. 246-255 ◽  
Author(s):  
Pratap Karki ◽  
Angelo Meliton ◽  
Albert Sitikov ◽  
Yufeng Tian ◽  
Tomomi Ohmura ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction

scholarly journals Pigment Epithelium-Derived Factor Induces Endothelial Barrier Dysfunction via p38/MAPK Phosphorylation

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ting He ◽  
Liping Zhao ◽  
Dongxia Zhang ◽  
Qiong Zhang ◽  
Jiezhi Jia ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Umbilical Vein ◽  
Pigment Epithelium ◽  
Endothelial Barrier ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Edema Formation ◽  
Endothelial Barrier Dysfunction ◽  
Pigment Epithelium Derived Factor

Endothelial barrier dysfunction, which is a serious problem that occurs in various inflammatory conditions, permits extravasation of serum components into the surrounding tissues, leading to edema formation and organ failure. Pigment epithelium-derived factor (PEDF), which is a major endogenous antagonist, has been implicated in diverse biological process, but its role in endothelial barrier dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF using human umbilical vein endothelial cells (HUVECs)in vitro. Our results demonstrated that exogenous PEDF activated p38/MAPK signalling pathway in a dose- and time-dependent manner and induced vascular hyperpermeability as measured by the markedly increased FITC-dextran leakage and the decreased transendothelial electrical resistance (TER) across the monolayer cells, which was accompanied by microtubules (MTs) disassembly and F-actin rearrangement. However, the aforementioned alterations can be arrested by the application of low concentration of p38/MAPK inhibitor SB203580. These results reveal a novel role for PEDF as a potential vasoactive substance in inducing hyperpermeability. Furthermore, our results suggest that PEDF and p38/MAPK may serve as therapeutic targets for maintaining vascular integrity.

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