YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization

Qiong Luo, Jing Luo, Yanlin Wang Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of ChinaCorrespondence: Yanlin WangDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Repub...

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Autores principales:	Luo Q, Luo J, Wang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	yes-associated protein macrophage polarization pulmonary inflammation mechanical ventilation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5fa5bd8d75f546dea9b5f70536a4c7c5
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spelling	oai:doaj.org-article:5fa5bd8d75f546dea9b5f70536a4c7c52021-12-02T15:06:10ZYAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization1178-7031https://doaj.org/article/5fa5bd8d75f546dea9b5f70536a4c7c52020-12-01T00:00:00Zhttps://www.dovepress.com/yap-deficiency-attenuates-pulmonary-injury-following-mechanical-ventil-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Qiong Luo, Jing Luo, Yanlin Wang Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of ChinaCorrespondence: Yanlin WangDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of ChinaEmail ylwang917@163.comBackground: Evidences indicate that the balance between macrophage M1 and M2 polarization is essential for the regulation of pulmonary inflammation during mechanical ventilation (MV). Yes-associated protein (YAP) is a key component of the Hippo pathway and was suggested to regulate macrophage polarization. This study was designed to investigate whether YAP contributes to pulmonary inflammation during MV.Methods: Wild-type and macrophage YAP knockout mice were mechanically ventilated for 12 hours to induce pulmonary injuries. At the end of MV, animals were sacrificed for pulmonary tissue collection and macrophage isolation. In addition, the induction of macrophage polarization was performed in isolated macrophages with or without YAP overexpression in vitro. Pulmonary injuries, YAP expression, macrophage polarization and cytokines were measured.Results: Here, we show that MV induces lung injury together with pulmonary inflammation as well as upregulated YAP expressions in pulmonary macrophages. In addition, our results indicate that YAP deficiency in macrophages attenuates pulmonary injury, accompanied with decreased production of pro-inflammatory cytokines including IL (interleukin)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α). Moreover, both in vivo and in vitro studies indicate that YAP deficiency enhances M2 polarization while inhibits M1 polarization. In contrast, YAP overexpression inhibits the induction of M2 polarization but improves M1 polarization.Conclusion: Our results report for the first time that the induction of YAP in macrophages contributes to pulmonary inflammation during MV through the regulation of M1/M2 polarization.Keywords: yes-associated protein, macrophage polarization, pulmonary inflammation, mechanical ventilationLuo QLuo JWang YDove Medical Pressarticleyes-associated proteinmacrophage polarizationpulmonary inflammationmechanical ventilationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 1279-1290 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	yes-associated protein macrophage polarization pulmonary inflammation mechanical ventilation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	yes-associated protein macrophage polarization pulmonary inflammation mechanical ventilation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Luo Q Luo J Wang Y YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
description	Qiong Luo, Jing Luo, Yanlin Wang Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of ChinaCorrespondence: Yanlin WangDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of ChinaEmail ylwang917@163.comBackground: Evidences indicate that the balance between macrophage M1 and M2 polarization is essential for the regulation of pulmonary inflammation during mechanical ventilation (MV). Yes-associated protein (YAP) is a key component of the Hippo pathway and was suggested to regulate macrophage polarization. This study was designed to investigate whether YAP contributes to pulmonary inflammation during MV.Methods: Wild-type and macrophage YAP knockout mice were mechanically ventilated for 12 hours to induce pulmonary injuries. At the end of MV, animals were sacrificed for pulmonary tissue collection and macrophage isolation. In addition, the induction of macrophage polarization was performed in isolated macrophages with or without YAP overexpression in vitro. Pulmonary injuries, YAP expression, macrophage polarization and cytokines were measured.Results: Here, we show that MV induces lung injury together with pulmonary inflammation as well as upregulated YAP expressions in pulmonary macrophages. In addition, our results indicate that YAP deficiency in macrophages attenuates pulmonary injury, accompanied with decreased production of pro-inflammatory cytokines including IL (interleukin)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α). Moreover, both in vivo and in vitro studies indicate that YAP deficiency enhances M2 polarization while inhibits M1 polarization. In contrast, YAP overexpression inhibits the induction of M2 polarization but improves M1 polarization.Conclusion: Our results report for the first time that the induction of YAP in macrophages contributes to pulmonary inflammation during MV through the regulation of M1/M2 polarization.Keywords: yes-associated protein, macrophage polarization, pulmonary inflammation, mechanical ventilation
format	article
author	Luo Q Luo J Wang Y
author_facet	Luo Q Luo J Wang Y
author_sort	Luo Q
title	YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
title_short	YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
title_full	YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
title_fullStr	YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
title_full_unstemmed	YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
title_sort	yap deficiency attenuates pulmonary injury following mechanical ventilation through the regulation of m1/m2 macrophage polarization
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/5fa5bd8d75f546dea9b5f70536a4c7c5
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YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization

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