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WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice
The hexapeptide WKYMVm, which is a strong formyl peptide receptor (FPR) 2 agonist, exhibits pro-angiogenic, anti-inflammatory and anti-apoptotic properties. However, its therapeutic efficacy in bronchopulmonary dysplasia (BPD) has not been tested to date. Here, we investigated whether WKYMVm attenua...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497690/ https://www.ncbi.nlm.nih.gov/pubmed/31048743 http://dx.doi.org/10.1038/s41598-019-43321-4 |
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author | Kim, Young Eun Park, Won Soon Ahn, So Yoon Sung, Dong Kyung Sung, Se In Kim, Jae Ho Chang, Yun Sil |
author_facet | Kim, Young Eun Park, Won Soon Ahn, So Yoon Sung, Dong Kyung Sung, Se In Kim, Jae Ho Chang, Yun Sil |
author_sort | Kim, Young Eun |
collection | PubMed |
description | The hexapeptide WKYMVm, which is a strong formyl peptide receptor (FPR) 2 agonist, exhibits pro-angiogenic, anti-inflammatory and anti-apoptotic properties. However, its therapeutic efficacy in bronchopulmonary dysplasia (BPD) has not been tested to date. Here, we investigated whether WKYMVm attenuates hyperoxia-induced lung inflammation and ensuing injuries by upregulating FPR2. The proliferation and tube formation ability of human umbilical vein endothelial cells (HUVECs), along with the level of extracellular signal regulated kinase (ERK) phosphorylation, were evaluated in vitro. Newborn mice were randomly exposed to 80% oxygen or room air for 14 days starting at birth. WKYMVm (2.5 mg/kg) was intraperitoneally administrated daily from postnatal day (P) 5 to P8. At P14, mice were sacrificed for histopathological and morphometric analyses. Along with upregulation of FPR2 and p-ERK, WKYMVm promoted HUVEC cell proliferation and tube formation in vitro. Additionally, WKYMVm promoted proliferation of human pulmonary microvascular endothelial cells (HULEC-5a) and murine pulmonary endothelial and epithelial cells in vitro. WKYMVm significantly attenuated hyperoxia-induced lung inflammation, as evidenced by increased inflammatory cytokines, neutrophils, and alveolar macrophages, and resultant lung injuries, which included impaired alveolarization and angiogenesis, an increased number of apoptotic cells, and reduced levels of growth factors in vivo, such as vascular endothelial growth factor and hepatocyte growth factor. WKYMVm attenuates hyperoxia-induced lung injuries and lung inflammation by upregulating FPR2 and p-ERK. |
format | Online Article Text |
id | pubmed-6497690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64976902019-05-17 WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice Kim, Young Eun Park, Won Soon Ahn, So Yoon Sung, Dong Kyung Sung, Se In Kim, Jae Ho Chang, Yun Sil Sci Rep Article The hexapeptide WKYMVm, which is a strong formyl peptide receptor (FPR) 2 agonist, exhibits pro-angiogenic, anti-inflammatory and anti-apoptotic properties. However, its therapeutic efficacy in bronchopulmonary dysplasia (BPD) has not been tested to date. Here, we investigated whether WKYMVm attenuates hyperoxia-induced lung inflammation and ensuing injuries by upregulating FPR2. The proliferation and tube formation ability of human umbilical vein endothelial cells (HUVECs), along with the level of extracellular signal regulated kinase (ERK) phosphorylation, were evaluated in vitro. Newborn mice were randomly exposed to 80% oxygen or room air for 14 days starting at birth. WKYMVm (2.5 mg/kg) was intraperitoneally administrated daily from postnatal day (P) 5 to P8. At P14, mice were sacrificed for histopathological and morphometric analyses. Along with upregulation of FPR2 and p-ERK, WKYMVm promoted HUVEC cell proliferation and tube formation in vitro. Additionally, WKYMVm promoted proliferation of human pulmonary microvascular endothelial cells (HULEC-5a) and murine pulmonary endothelial and epithelial cells in vitro. WKYMVm significantly attenuated hyperoxia-induced lung inflammation, as evidenced by increased inflammatory cytokines, neutrophils, and alveolar macrophages, and resultant lung injuries, which included impaired alveolarization and angiogenesis, an increased number of apoptotic cells, and reduced levels of growth factors in vivo, such as vascular endothelial growth factor and hepatocyte growth factor. WKYMVm attenuates hyperoxia-induced lung injuries and lung inflammation by upregulating FPR2 and p-ERK. Nature Publishing Group UK 2019-05-02 /pmc/articles/PMC6497690/ /pubmed/31048743 http://dx.doi.org/10.1038/s41598-019-43321-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kim, Young Eun Park, Won Soon Ahn, So Yoon Sung, Dong Kyung Sung, Se In Kim, Jae Ho Chang, Yun Sil WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
title | WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
title_full | WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
title_fullStr | WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
title_full_unstemmed | WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
title_short | WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
title_sort | wkymvm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497690/ https://www.ncbi.nlm.nih.gov/pubmed/31048743 http://dx.doi.org/10.1038/s41598-019-43321-4 |
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