Cargando…
Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction
Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activatio...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676476/ https://www.ncbi.nlm.nih.gov/pubmed/29209448 http://dx.doi.org/10.1155/2017/4082102 |
_version_ | 1783277073646747648 |
---|---|
author | Zhang, Weijin Zhang, Yaoyuan Guo, Xiaohua Zeng, Zhenhua Wu, Jie Liu, Yanan He, Jing Wang, Ruiting Huang, Qiaobing Chen, Zhongqing |
author_facet | Zhang, Weijin Zhang, Yaoyuan Guo, Xiaohua Zeng, Zhenhua Wu, Jie Liu, Yanan He, Jing Wang, Ruiting Huang, Qiaobing Chen, Zhongqing |
author_sort | Zhang, Weijin |
collection | PubMed |
description | Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1 with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber stress, and disruption of VE-cadherin distribution. In pulmonary microvascular vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon LPS, while Sirt1 was preserved in a receptor of advanced glycation end product-knockout mice. The RAGE antibody could also diminish the downregulation and ubiquitination of Sirt1 in LPS-exposed human umbilical vein endothelial cells. An LPS-induced decrease in Sirt1 activity was attenuated by the RAGE antibody and TLR4 inhibitor. In vivo study also demonstrated the attenuating role of Sirt1 and RAGE knockout in LPS-induced increases in dextran leakage of mesenteric venules. Furthermore, activation of Sirt1 prevented LPS-induced decreases in the activity and expression of superoxide dismutase 2, as well as the increases in NADPH oxidase 4 and reactive oxygen species, while inhibition of Sirt1 aggravated the SOD2 decline. It also demonstrated that Sirt1-deacetylated p53 is required for p53 inactivation, which reversed the downregulation of β-catenin caused by LPS. |
format | Online Article Text |
id | pubmed-5676476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-56764762017-12-05 Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction Zhang, Weijin Zhang, Yaoyuan Guo, Xiaohua Zeng, Zhenhua Wu, Jie Liu, Yanan He, Jing Wang, Ruiting Huang, Qiaobing Chen, Zhongqing Oxid Med Cell Longev Research Article Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1 with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber stress, and disruption of VE-cadherin distribution. In pulmonary microvascular vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon LPS, while Sirt1 was preserved in a receptor of advanced glycation end product-knockout mice. The RAGE antibody could also diminish the downregulation and ubiquitination of Sirt1 in LPS-exposed human umbilical vein endothelial cells. An LPS-induced decrease in Sirt1 activity was attenuated by the RAGE antibody and TLR4 inhibitor. In vivo study also demonstrated the attenuating role of Sirt1 and RAGE knockout in LPS-induced increases in dextran leakage of mesenteric venules. Furthermore, activation of Sirt1 prevented LPS-induced decreases in the activity and expression of superoxide dismutase 2, as well as the increases in NADPH oxidase 4 and reactive oxygen species, while inhibition of Sirt1 aggravated the SOD2 decline. It also demonstrated that Sirt1-deacetylated p53 is required for p53 inactivation, which reversed the downregulation of β-catenin caused by LPS. Hindawi 2017 2017-10-25 /pmc/articles/PMC5676476/ /pubmed/29209448 http://dx.doi.org/10.1155/2017/4082102 Text en Copyright © 2017 Weijin Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Weijin Zhang, Yaoyuan Guo, Xiaohua Zeng, Zhenhua Wu, Jie Liu, Yanan He, Jing Wang, Ruiting Huang, Qiaobing Chen, Zhongqing Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction |
title | Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction |
title_full | Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction |
title_fullStr | Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction |
title_full_unstemmed | Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction |
title_short | Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction |
title_sort | sirt1 protects endothelial cells against lps-induced barrier dysfunction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676476/ https://www.ncbi.nlm.nih.gov/pubmed/29209448 http://dx.doi.org/10.1155/2017/4082102 |
work_keys_str_mv | AT zhangweijin sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT zhangyaoyuan sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT guoxiaohua sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT zengzhenhua sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT wujie sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT liuyanan sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT hejing sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT wangruiting sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT huangqiaobing sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction AT chenzhongqing sirt1protectsendothelialcellsagainstlpsinducedbarrierdysfunction |