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

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

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7 Citations (Scopus)

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.

Original languageEnglish
Article number6737
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

All Science Journal Classification (ASJC) codes

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    Chae, H. S., You, B. H., Kim, D. Y., Lee, H., Ko, H. W., Ko, H. J., Choi, Y. H., Choi, S. S., & Chin, Y. W. (2018). Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network. Scientific reports, 8(1), [6737]. https://doi.org/10.1038/s41598-018-24935-6