Abstract
BackgroundAugmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway.MethodsThe level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively.ResultsDuring the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls.ConclusionWe demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury.
Highlights
Acute liver injury is a liver function abnormality that results from multiple reasons, such as viral infection, abuse of drugs or alcohol, ingestion of toxic substance and so on [1, 2]
We demonstrated that Augmenter of liver regeneration (ALR) ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury
To investigate the role of ALR in acute liver injury, we examined the expression of ALR in mice exposed to carbon tetrachloride (CCl4)
Summary
Acute liver injury is a liver function abnormality that results from multiple reasons, such as viral infection, abuse of drugs or alcohol, ingestion of toxic substance and so on [1, 2]. Augmenter of liver regeneration (ALR) is thought to be a hepatotrophic growth factor that is responsible for the extraordinary regenerative capacity of the mammalian liver [4]. A recent study found that unlike hepatocyte growth factor (HGF) or epidermal growth factor (EGF), ALR plays an important role in proliferation and antiapoptosis in a liver-specific manner [5, 6]. Song et al found that ALR might protect against CCl4-induced liver injury by reducing mitochondrial dysfunction and inhibiting oxidative stress [7]. The protective mechanism of ALR in liver injury needs to be further explored. Augmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
