Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network

Abstract Whole-transcriptome analysis and western blotting of sauchinone-treated HepG2 cells demonstrated that sauchinone regulated genes relevant to cholesterol metabolism and synthesis. In particular, it was found that the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) was dow...

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Autores principales:	Hee-Sung Chae, Byoung Hoon You, Dong-Yeop Kim, Hankyu Lee, Hyuk Wan Ko, Hyun-Jeong Ko, Young Hee Choi, Sun Shim Choi, Young-Won Chin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88c1acd2a8594bb8aeaab7ad3b865b1a
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spelling	oai:doaj.org-article:88c1acd2a8594bb8aeaab7ad3b865b1a2021-12-02T15:08:28ZSauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network10.1038/s41598-018-24935-62045-2322https://doaj.org/article/88c1acd2a8594bb8aeaab7ad3b865b1a2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24935-6https://doaj.org/toc/2045-2322Abstract Whole-transcriptome analysis and western blotting of sauchinone-treated HepG2 cells demonstrated that sauchinone regulated genes relevant to cholesterol metabolism and synthesis. In particular, it was found that the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) was downregulated, and the expression of low density lipoprotein receptor (LDLR) was upregulated in sauchinone-treated HepG2 cells. Consequently, LDL-cholesterol (LDL-C) uptake was increased. As a transcriptional regulator of PCSK9 expression, sterol regulatory elements binding protein-2 (SREBP-2) was proposed by transcriptome analysis and western blotting. Oral administration of sauchinone increased hepatic LDLR through PCSK9 inhibition in obese mice and showed the reduced serum LDL-C levels and downstream targets of SREBP-2. Thus, it is evident that sauchinone reduces hepatic steatosis by downregulating the expression of hepatic PCSK9 via SREBP-2.Hee-Sung ChaeByoung Hoon YouDong-Yeop KimHankyu LeeHyuk Wan KoHyun-Jeong KoYoung Hee ChoiSun Shim ChoiYoung-Won ChinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hee-Sung Chae Byoung Hoon You Dong-Yeop Kim Hankyu Lee Hyuk Wan Ko Hyun-Jeong Ko Young Hee Choi Sun Shim Choi Young-Won Chin Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
description	Abstract Whole-transcriptome analysis and western blotting of sauchinone-treated HepG2 cells demonstrated that sauchinone regulated genes relevant to cholesterol metabolism and synthesis. In particular, it was found that the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) was downregulated, and the expression of low density lipoprotein receptor (LDLR) was upregulated in sauchinone-treated HepG2 cells. Consequently, LDL-cholesterol (LDL-C) uptake was increased. As a transcriptional regulator of PCSK9 expression, sterol regulatory elements binding protein-2 (SREBP-2) was proposed by transcriptome analysis and western blotting. Oral administration of sauchinone increased hepatic LDLR through PCSK9 inhibition in obese mice and showed the reduced serum LDL-C levels and downstream targets of SREBP-2. Thus, it is evident that sauchinone reduces hepatic steatosis by downregulating the expression of hepatic PCSK9 via SREBP-2.
format	article
author	Hee-Sung Chae Byoung Hoon You Dong-Yeop Kim Hankyu Lee Hyuk Wan Ko Hyun-Jeong Ko Young Hee Choi Sun Shim Choi Young-Won Chin
author_facet	Hee-Sung Chae Byoung Hoon You Dong-Yeop Kim Hankyu Lee Hyuk Wan Ko Hyun-Jeong Ko Young Hee Choi Sun Shim Choi Young-Won Chin
author_sort	Hee-Sung Chae
title	Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
title_short	Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
title_full	Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
title_fullStr	Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
title_full_unstemmed	Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
title_sort	sauchinone controls hepatic cholesterol homeostasis by the negative regulation of pcsk9 transcriptional network
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/88c1acd2a8594bb8aeaab7ad3b865b1a
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Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network

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