期刊
ONCOTARGET
卷 6, 期 40, 页码 42530-42540出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6466
关键词
liver fibrosis; OEA; PPAR-alpha; TGF-beta 1; hepatic stellate cells; Pathology Section
资金
- National Natural Sciences Foundation of China [81373273, 81273371]
- Fundamental Research Funds for the Central Universities [20720150054]
- Scientific & Technological Key Projects of Fujian Province [2013N0020]
Oleoylethanolamide (OEA), an endocannabinoid-like molecule, was revealed to modulate lipid metabolism through a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) mediated mechanism. In present study, we further investigated the activities and mechanisms of OEA in ameliorating hepatic fibrosis in Sv/129 mice induced by a methionine choline-deficient (MCD) diet or thioacetamide (TAA) treatment. Liver fibrosis development was assessed by Hematoxylin-eosin and Sirius red staining. Treatment with OEA (5 mg/kg/day, intraperitoneal injection, i. p.) significantly attenuated the progress of liver fibrosis in both two experimental animal models by blocking the activation of hepatic stellate cells (HSCs). Gene expression analysis of hepatic tissues indicated that OEA inhibited the expression of alpha-smooth muscle action (alpha-SMA) and collagen matrix, fibrosis markers, and genes involved in inflammation and extracellular matrix remodeling. In vitro studies showed that OEA inhibited transforming growth factor beta 1-stimulated HSCs activation through suppressing Smad2/3 phosphorylation, alpha-SMA expression and myofibroblast transformation. These improvements could not be observed in PPAR-alpha knockout mice models with OEA administration, which suggested all the anti-fibrotic effects of OEA in vivo and in vitro were mediated by PPAR-alpha activation. Collectively, our results suggested that OEA exerted a pharmacological effect on modulating hepatic fibrosis development through the inhibition of HSCs activation in liver and therefore may be a potential therapeutic agent for liver fibrosis.
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