Docosahexaenoic acid inhibits hepatic stellate cell activation to attenuate liver fibrosis in a PPARγ-dependent manner

被引：20

作者：

He, Jianlin ^{[1
,2
]}

Hong, Bihong ^{[1
]}

Bian, Mianli ^{[2
]}

Jin, Huanhuan ^{[2
,3
]}

Chen, Junde ^{[1
]}

Shao, Jiangjuan ^{[2
]}

Zhang, Feng ^{[2
]}

Zheng, Shizhong ^{[2
]}

机构：

[1] Minist Nat Resources, Inst Oceanog 3, Xiamen 361005, Fujian, Peoples R China

[2] Nanjing Univ Chinese Med, Sch Pharm, Dept Pharmacol, Nanjing 210029, Jiangsu, Peoples R China

[3] Wannan Med Coll, Sch Pharm, Dept Pharmacol, Wuhu 241000, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2019年 / 75卷

基金：

中国国家自然科学基金;

关键词：

Docosahexaenoic acid; Liver fibrosis; Peroxisome proliferator-activated receptor gamma; Molecular docking; Hepatic stellate cells; Ligand activation; POLYUNSATURATED FATTY-ACIDS; RECEPTOR-GAMMA; GENE-EXPRESSION; LIGAND; PDGF; N-3; TRANSREPRESSION; P21(WAF1/CIP1); TROGLITAZONE; P18(INK4C);

D O I：

10.1016/j.intimp.2019.105816

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Docosahexaenoic acid (DHA) has been found to have a hepatoprotective effect. In this study, we investigated the role of peroxisome proliferator-activated receptor gamma (PPAR gamma) in DHA regulation of liver fibrosis. DHA was found to inhibit hepatic stellate cell (HSC)-LX2 cell viability and downregulate marker proteins of HSC activation. Furthermore, DHA induced cell cycle arrest at G1 phase in HSCs. Antagonism of PPAR gamma by GW9662 abrogated the effects of DHA on HSCs. Computer-aided molecular docking predicted that DHA bound to PPAR gamma via hydrogen bonding with residues Ser289, His323, Tyr473, and His499. We overexpressed Ser289 mutant PPAR gamma in HSC-LX2 cells and investigated fibrotic marker modulation, and found that DHA effects on HSCs were diminished. Thus, bonding with the Ser289 residue might be indispensable for DHA to activate PPAR gamma to exert its inhibiting effect on activated HSCs. Last, data from a CCl4-treated mouse model confirmed that PPAR gamma activation was required for DHA to attenuate liver fibrosis.

引用

页数：11

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