| Title |
Lipopolysaccharide-induced caveolin-1 phosphorylation-dependent increase in transcellular permeability precedes the increase in paracellular permeability
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2015
|
| DOI | 10.2147/dddt.s77646 |
| Pubmed ID | |
| Authors |
Nan Wang, Dan Zhang, Gengyun Sun, Hong Zhang, Qinghai You, Min Shao, Yang Yue |
| Abstract |
Lipopolysaccharide (LPS) was shown to induce an increase in caveolin-1 (Cav-1) expression in endothelial cells; however, the mechanisms regarding this response and the consequences on caveolae-mediated transcellular transport have not been completely investigated. This study aims to investigate the role of LPS-induced Cav-1 phosphorylation in pulmonary microvascular permeability in pulmonary microvascular endothelial cells (PMVECs). Rat PMVECs were isolated, cultured, and identified. Endocytosis experiments were employed to stain the nuclei by DAPI, and images were obtained with a fluorescence microscope. Permeability of endothelial cultures was measured to analyze the barrier function of endothelial monolayer. Western blot assay was used to examine the expression of Cav-1, pCav-1, triton-insoluble Cav-1, and triton-soluble Cav-1 protein. The LPS treatment induced phosphorylation of Cav-1, but did not alter the total Cav-1 level till 60 min in both rat and human PMVECs. LPS treatment also increased the triton-insoluble Cav-1 level, which peaked 15 min after LPS treatment in both rat and human PMVECs. LPS treatment increases the intercellular cell adhesion molecule-1 expression. Src inhibitors, including PP2, PP1, Saracatinib, and Quercetin, partially inhibited LPS-induced phosphorylation of Cav-1. In addition, both PP2 and caveolae disruptor MβCD inhibited LPS-induced increase of triton-insoluble Cav-1. LPS induces permeability by activating interleukin-8 and vascular endothelial growth factor and targeting other adhesion markers, such as ZO-1 and occludin. LPS treatment also significantly increased the endocytosis of albumin, which could be blocked by PP2 or MβCD. Furthermore, LPS treatment for 15 min significantly elevated Evans Blue-labeled BSA transport in advance of a decrease in transendothelial electrical resistance of PMVEC monolayer at this time point. After LPS treatment for 30 min, transendothelial electrical resistance decreased significantly. Moreover, PP2 and MβCD blocked LPS-induced increase in Evans Blue-labeled BSA level. Our study demonstrates that LPS-induced Cav-1 phosphorylation may lead to the increase of transcellular permeability prior to the increase of paracellular permeability in a Src-dependent manner. Thus, LPS-induced Cav-1 phosphorylation may be a therapeutic target for the treatment of inflammatory lung disease associated with elevated microvascular permeability. |
Mendeley readers
The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 21 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 38% |
| Student > Master | 5 | 24% |
| Researcher | 1 | 5% |
| Student > Bachelor | 1 | 5% |
| Unknown | 6 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 5 | 24% |
| Biochemistry, Genetics and Molecular Biology | 4 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 10% |
| Computer Science | 2 | 10% |
| Immunology and Microbiology | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 6 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 March 2016.
All research outputs
#17,285,668
of 25,373,627 outputs
Outputs from Drug Design, Development and Therapy
#1,105
of 2,268 outputs
Outputs of similar age
#165,170
of 276,419 outputs
Outputs of similar age from Drug Design, Development and Therapy
#76
of 151 outputs
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