Author:
Wu Shaobo,Wu Yao,Lin Lan,Ruan Changshun,Li Fang,Chen Rong,Du Hongxin,Zhang Xianxiang,Luo Xiaohe
Abstract
AbstractClinical studies have shown that osteoprotegerin (OPG) is reduced in patients with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms are unclear. The current study focuses on the role of OPG in the NASH pathogenesis. OPG knockout mice and wild-type control mice fed a methionine choline-deficient diet (MCD) for 4 weeks resulted in an animal model of NASH. Measurement of triglycerides (TG) in serum and liver to assess steatosis. Hematoxylin eosin (HE), Sirius Red and Masson staining were used to assess the liver damage. Transcriptome sequencing analysis, qPCR and western blot were to analyze changes in lipid metabolism and inflammation-related indicators in the liver. In vivo knockout of OPG resulted in a reduction of TG levels in the liver and a significant increase in serum ALT and AST. The expression of inflammatory factors and fibrosis genes was significantly upregulated in the livers of OPG knockout mice. Transcriptome sequencing analysis showed that OPG knockout significantly enhanced MCD diet-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Mechanistically, OPG may inhibit MAPK signaling pathway activity by upregulating the expression of dual specificity phosphatase 14 (DUSP14), thereby reducing inflammatory injury. OPG could regulate the activity of the MAPK signaling pathway via DUSP14, thus regulating the expression of some inflammatory factors in NASH, it may be a promising target for the treatment of NASH.
Funder
Natural Science Foundation of Chongqing
Wan Zhou District Science and Technology Planning Project
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Fundamental Research Funds for the Central Universities
Doctoral Research Fund of Chongqing University Three Gorges Central Hospital
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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