Fc-apelin fusion protein attenuates lipopolysaccharide-induced liver injury in mice
Authors:
Open Access
- 30 July 2018
- journal article
- research article
- Published by Springer Nature in Scientific Reports
- Vol. 8 (1) , 1-8
Abstract
Apelin is a peptide hormone with anti-oxidative and anti-inflammatory activities and is proposed to be a potential therapeutic for many disease conditions, including sepsis. However, short in vivo half-life of the apelin peptide would limit its potential clinical applications. This study aims to investigate the effects of Fc-apelin, a novel long-acting apelin fusion protein, on lipopolysaccharide (LPS)-induced liver injury. Liver injury was induced by systemic injection of LPS in mice. Hepatoprotective activities of Fc-apelin against inflammation were evaluated in LPS mice and/or hepatoma Huh-7 cells with respect to serum ALT, apoptosis, oxidative stress, macrophage infiltration and gene expression. We found that LPS induced systemic inflammation and liver damage. Co-administration of Fc-apelin significantly attenuated serum ALT elevation, diminished LPS-induced apoptosis and ROS production in the liver and in Huh-7 cells, mitigated hepatic macrophage infiltration, and reduced TNFα and IL-6 gene expression. Collectively, Fc-apelin fusion protein exerts protective effects against LPS-induced liver damage and may serve as a potential therapeutic for endotoxin-induced liver injury.Keywords
Funding Information
- Maryland Stem Cell Research Fund
This publication has 45 references indexed in Scilit:
- The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasisJournal of Endocrinology, 2013
- Inhibition of IκB kinase reduces the multiple organ dysfunction caused by sepsis in the mouseDisease Models & Mechanisms, 2013
- Protective effect of apelin on cultured rat bone marrow mesenchymal stem cells against apoptosisStem Cell Research, 2012
- Hypoxia and proinflammatory factors upregulate apelin receptor expression in human stellate cells and hepatocytesGut, 2011
- Reactive oxygen and mechanisms of inflammatory liver injury: Present conceptsJournal of Gastroenterology and Hepatology, 2011
- Activation of catalase by apelin prevents oxidative stress‐linked cardiac hypertrophyFEBS Letters, 2010
- Alanine aminotransferase isoenzymes: Molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity #Hepatology, 2009
- Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic ComplicationsPLOS Medicine, 2006
- Toll-like receptor signallingNature Reviews Immunology, 2004
- Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ ReceptorBiochemical and Biophysical Research Communications, 1998