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Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury
BACKGROUND: Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI d...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595601/ https://www.ncbi.nlm.nih.gov/pubmed/31242908 http://dx.doi.org/10.1186/s12931-019-1099-6 |
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author | Yang, Nana Tian, Hua Zhan, Enxin Zhai, Lei Jiao, Peng Yao, Shutong Lu, Guohua Mu, Qingjie Wang, Juan Zhao, Aihua Zhou, Yadong Qin, Shucun |
author_facet | Yang, Nana Tian, Hua Zhan, Enxin Zhai, Lei Jiao, Peng Yao, Shutong Lu, Guohua Mu, Qingjie Wang, Juan Zhao, Aihua Zhou, Yadong Qin, Shucun |
author_sort | Yang, Nana |
collection | PubMed |
description | BACKGROUND: Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model. METHODS: LPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved. RESULTS: Rev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS. CONCLUSIONS: These findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1099-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6595601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65956012019-08-07 Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury Yang, Nana Tian, Hua Zhan, Enxin Zhai, Lei Jiao, Peng Yao, Shutong Lu, Guohua Mu, Qingjie Wang, Juan Zhao, Aihua Zhou, Yadong Qin, Shucun Respir Res Research BACKGROUND: Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model. METHODS: LPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved. RESULTS: Rev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS. CONCLUSIONS: These findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1099-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-26 2019 /pmc/articles/PMC6595601/ /pubmed/31242908 http://dx.doi.org/10.1186/s12931-019-1099-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Yang, Nana Tian, Hua Zhan, Enxin Zhai, Lei Jiao, Peng Yao, Shutong Lu, Guohua Mu, Qingjie Wang, Juan Zhao, Aihua Zhou, Yadong Qin, Shucun Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury |
title | Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury |
title_full | Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury |
title_fullStr | Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury |
title_full_unstemmed | Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury |
title_short | Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury |
title_sort | reverse-d-4f improves endothelial progenitor cell function and attenuates lps-induced acute lung injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595601/ https://www.ncbi.nlm.nih.gov/pubmed/31242908 http://dx.doi.org/10.1186/s12931-019-1099-6 |
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