Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism

MiR-30a-5p plays an important role in various cardiovascular diseases, but its effect in atherosclerosis has not been reported. Apolipoprotein E-deficient (Apo E−/−) mice were used to investigate the role of miR-30a-5p in atherosclerosis, and the underlying mechanism was investigated in vivo and in ...

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Autores principales:	Fei Song, Jing-Zhou Li, Yao Wu, Wei-Yin Wu, Yan Wang, Gang Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	miR-30a-5p macrophage M1/M2 polarization NEDD4L ubiquitin ABCA1 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1768eefb880247b091015608b9f905f5
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spelling	oai:doaj.org-article:1768eefb880247b091015608b9f905f52021-11-22T04:23:50ZUbiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism2162-253110.1016/j.omtn.2021.10.030https://doaj.org/article/1768eefb880247b091015608b9f905f52021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002730https://doaj.org/toc/2162-2531MiR-30a-5p plays an important role in various cardiovascular diseases, but its effect in atherosclerosis has not been reported. Apolipoprotein E-deficient (Apo E−/−) mice were used to investigate the role of miR-30a-5p in atherosclerosis, and the underlying mechanism was investigated in vivo and in vitro. The fluorescence in situ hybridization test revealed that miR-30a-5p was expressed in Apo E−/− mice lesions. Nevertheless, in RAW264.7 macrophages, the expression of miR-30a-5p was reduced by lipopolysaccharide (LPS) or oxidized low-density lipoprotein. MiR-30a-5p-ago-treated Apo E−/− mice significantly reduced lesion areas in the aorta and aortic root, reduced levels of lipoprotein and pro-inflammatory cytokines, and increased levels of anti-inflammatory cytokines. The ratio of M1/M2 macrophages was decreased in miR-30a-5p-ago-treated Apo E−/− mice and LPS-treated RAW264.7 macrophages by the regulation of Smad-1/2 phosphorylation. MiR-30a-5p reduced lipid uptake in oxidized low-density lipoprotein-treated macrophages by regulating the expression of PPAR-γ, ABCA1, ABCG1, LDLR, and PCSK9. Ubiquitinated ligase NEDD4L was identified as a target of miR-30a-5p. Interestingly, knockdown of NEDD4L decreased the M1/M2 ratio and oxidized low-density lipoprotein uptake in macrophages by inhibiting the ubiquitination of PPAR-γ and phosphorylation of Smad-1/2 and regulating ABCA1, ABCG1, LDLR, and PCSK9. We demonstrated a novel effect and mechanism of miR-30a-5p in atherosclerosis.Fei SongJing-Zhou LiYao WuWei-Yin WuYan WangGang LiElsevierarticlemiR-30a-5pmacrophageM1/M2 polarizationNEDD4LubiquitinABCA1Therapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1303-1317 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-30a-5p macrophage M1/M2 polarization NEDD4L ubiquitin ABCA1 Therapeutics. Pharmacology RM1-950
spellingShingle	miR-30a-5p macrophage M1/M2 polarization NEDD4L ubiquitin ABCA1 Therapeutics. Pharmacology RM1-950 Fei Song Jing-Zhou Li Yao Wu Wei-Yin Wu Yan Wang Gang Li Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
description	MiR-30a-5p plays an important role in various cardiovascular diseases, but its effect in atherosclerosis has not been reported. Apolipoprotein E-deficient (Apo E−/−) mice were used to investigate the role of miR-30a-5p in atherosclerosis, and the underlying mechanism was investigated in vivo and in vitro. The fluorescence in situ hybridization test revealed that miR-30a-5p was expressed in Apo E−/− mice lesions. Nevertheless, in RAW264.7 macrophages, the expression of miR-30a-5p was reduced by lipopolysaccharide (LPS) or oxidized low-density lipoprotein. MiR-30a-5p-ago-treated Apo E−/− mice significantly reduced lesion areas in the aorta and aortic root, reduced levels of lipoprotein and pro-inflammatory cytokines, and increased levels of anti-inflammatory cytokines. The ratio of M1/M2 macrophages was decreased in miR-30a-5p-ago-treated Apo E−/− mice and LPS-treated RAW264.7 macrophages by the regulation of Smad-1/2 phosphorylation. MiR-30a-5p reduced lipid uptake in oxidized low-density lipoprotein-treated macrophages by regulating the expression of PPAR-γ, ABCA1, ABCG1, LDLR, and PCSK9. Ubiquitinated ligase NEDD4L was identified as a target of miR-30a-5p. Interestingly, knockdown of NEDD4L decreased the M1/M2 ratio and oxidized low-density lipoprotein uptake in macrophages by inhibiting the ubiquitination of PPAR-γ and phosphorylation of Smad-1/2 and regulating ABCA1, ABCG1, LDLR, and PCSK9. We demonstrated a novel effect and mechanism of miR-30a-5p in atherosclerosis.
format	article
author	Fei Song Jing-Zhou Li Yao Wu Wei-Yin Wu Yan Wang Gang Li
author_facet	Fei Song Jing-Zhou Li Yao Wu Wei-Yin Wu Yan Wang Gang Li
author_sort	Fei Song
title	Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
title_short	Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
title_full	Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
title_fullStr	Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
title_full_unstemmed	Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
title_sort	ubiquitinated ligation protein nedd4l participates in mir-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1768eefb880247b091015608b9f905f5
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_version_	1718418207650349056

Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism

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