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

Autor: 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
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-018-24935-6
Popis: 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.
Databáze: Directory of Open Access Journals
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