A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis

Abstract Activation of the endothelium by pro-inflammatory stimuli plays a key role in the pathogenesis of a multitude of vascular diseases. Angiogenesis is a crucial component of the vascular response associated with inflammatory signaling. The CD40/CD40 ligand dyad in endothelial cells (EC) has a...

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Autores principales:	Aram Lee, Irinna Papangeli, Youngsook Park, Ha-neul Jeong, Jihea Choi, Hyesoo Kang, Ha-neul Jo, Jongmin Kim, Hyung J. Chun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c9d724390ac74109ab3a7959e35b8668
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spelling	oai:doaj.org-article:c9d724390ac74109ab3a7959e35b86682021-12-02T16:07:02ZA PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis10.1038/s41598-017-02852-42045-2322https://doaj.org/article/c9d724390ac74109ab3a7959e35b86682017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02852-4https://doaj.org/toc/2045-2322Abstract Activation of the endothelium by pro-inflammatory stimuli plays a key role in the pathogenesis of a multitude of vascular diseases. Angiogenesis is a crucial component of the vascular response associated with inflammatory signaling. The CD40/CD40 ligand dyad in endothelial cells (EC) has a central role in promoting vascular inflammatory response; however, the molecular mechanism underlying this component of inflammation and angiogenesis is not fully understood. Here we report a novel microRNA mediated suppression of endothelial CD40 expression. We found that CD40 is closely regulated by miR-424 and miR-503, which directly target its 3′ untranslated region. Pro-inflammatory stimuli led to increased endothelial CD40 expression, at least in part due to decreased miR-424 and miR-503 expression. In addition, miR-424 and miR-503 reduced LPS induced EC sprouting, migration and tube formation. Moreover, we found that miR-424 and miR-503 expression is directly regulated by peroxisome proliferator-activated receptor gamma (PPARγ), whose endothelial expression and activity are decreased in response to inflammatory factors. Finally, we demonstrate that mice with endothelial-specific deletion of miR-322 (miR-424 ortholog) and miR-503 have augmented angiogenic response to LPS in a Matrigel plug assay. Overall, these studies identify a PPARγ-dependent miR-424/503-CD40 signaling axis that is critical for regulation of inflammation mediated angiogenesis.Aram LeeIrinna PapangeliYoungsook ParkHa-neul JeongJihea ChoiHyesoo KangHa-neul JoJongmin KimHyung J. ChunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aram Lee Irinna Papangeli Youngsook Park Ha-neul Jeong Jihea Choi Hyesoo Kang Ha-neul Jo Jongmin Kim Hyung J. Chun A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
description	Abstract Activation of the endothelium by pro-inflammatory stimuli plays a key role in the pathogenesis of a multitude of vascular diseases. Angiogenesis is a crucial component of the vascular response associated with inflammatory signaling. The CD40/CD40 ligand dyad in endothelial cells (EC) has a central role in promoting vascular inflammatory response; however, the molecular mechanism underlying this component of inflammation and angiogenesis is not fully understood. Here we report a novel microRNA mediated suppression of endothelial CD40 expression. We found that CD40 is closely regulated by miR-424 and miR-503, which directly target its 3′ untranslated region. Pro-inflammatory stimuli led to increased endothelial CD40 expression, at least in part due to decreased miR-424 and miR-503 expression. In addition, miR-424 and miR-503 reduced LPS induced EC sprouting, migration and tube formation. Moreover, we found that miR-424 and miR-503 expression is directly regulated by peroxisome proliferator-activated receptor gamma (PPARγ), whose endothelial expression and activity are decreased in response to inflammatory factors. Finally, we demonstrate that mice with endothelial-specific deletion of miR-322 (miR-424 ortholog) and miR-503 have augmented angiogenic response to LPS in a Matrigel plug assay. Overall, these studies identify a PPARγ-dependent miR-424/503-CD40 signaling axis that is critical for regulation of inflammation mediated angiogenesis.
format	article
author	Aram Lee Irinna Papangeli Youngsook Park Ha-neul Jeong Jihea Choi Hyesoo Kang Ha-neul Jo Jongmin Kim Hyung J. Chun
author_facet	Aram Lee Irinna Papangeli Youngsook Park Ha-neul Jeong Jihea Choi Hyesoo Kang Ha-neul Jo Jongmin Kim Hyung J. Chun
author_sort	Aram Lee
title	A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
title_short	A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
title_full	A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
title_fullStr	A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
title_full_unstemmed	A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
title_sort	pparγ-dependent mir-424/503-cd40 axis regulates inflammation mediated angiogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c9d724390ac74109ab3a7959e35b8668
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_version_	1718384804950441984

A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis

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