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Cilostazol Improves HFD-Induced Hepatic Steatosis by Upregulating Hepatic STAMP2 Expression through AMPK

Title
Cilostazol Improves HFD-Induced Hepatic Steatosis by Upregulating Hepatic STAMP2 Expression through AMPK
Author
남태규
Keywords
NONALCOHOLIC FATTY LIVER; ADIPOSE-TISSUE; IN-VITRO; INSULIN; DISEASE; STEATOHEPATITIS; INFLAMMATION; PROTEIN; ACTIVATION; INHIBITOR
Issue Date
2018-12
Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation
MOLECULAR PHARMACOLOGY, v. 94, No. 6, Page. 1401-1411
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly studied condition that can progress to end-stage liver disease. Although NAFLD was first described in 1980, a complete understanding of the mechanism and causes of this disease is still lacking. Six-transmembrane protein of prostate 2 (STAMP2) plays a role in integrating inflammatory and nutritional signals with metabolism. Our previous study suggested that STAMP2 may be a suitable target for treating NAFLD. In the current study, we performed a focused drug-screening and found that cilostazol could be a potential STAMP2 enhancer. Thus, we examined whether cilostazol alleviates NAFLD through STAMP2. The in vivo and in vitro pharmacological efficacies of cilostazol on STAMP2 expression and lipid accumulation were analyzed in NAFLD mice induced by high-fat diet (HFD) and in HepG2 cell lines treated by oleic acid (OA), respectively. Cilostazol increased the expression of STAMP2 through transcriptional regulation in vivo and in vitro. Cilostazol also dampened the STAMP2 downregulation caused by the HFD and by OA in vivo and in vitro, respectively. Cilostazol activated AMP-activated protein kinase (AMPK) in vivo and in vitro, and AMPK functions upstream of STAMP2, and reversed downregulation of STAMP2 expression through AMPK in the NAFLD model. Cilostazol ameliorates hepatic steatosis by enhancing hepatic STAMP2 expression through AMPK. Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD.
URI
http://molpharm.aspetjournals.org/content/94/6/1401http://repository.hanyang.ac.kr/handle/20.500.11754/105808
ISSN
0026-895X; 1521-0111
DOI
10.1124/mol.118.113217
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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