Abstract
Liver regeneration after partial hepatectomy (PH) is a highly orchestrated biological process in which synchronized hepatocyte proliferation is induced after massive liver mass loss. Hepatocyte proliferation could be regulated by multiple signals, such as miRNAs and autophagy, but underlying mechanism remains unclear. Here a functional miRNA during liver regeneration was identified and its underlying mechanism was delineated in vitro and in vivo. We found that miR-1907 was highly upregulated during liver regeneration after 2/3 PH at various timepoints. The level of miR-1907 was also increased in normal liver cell line treated with HGF at different concentrations. Functionally, miR-1907 enhanced hepatocyte proliferation in vitro and in vivo, and the liver/body weight ratio in miR-1907-overexpressed mice was significantly higher in comparison to the control mice after 2/3 PH. Forced expression of miR-1907 promoted autophagy activation of hepatocyte. Importantly, autophagy inhibition significantly attenuated miR-1907-induced hepatocyte proliferation and the liver/body weight ratio. Finally, GSK3β, a suppressor of autophagy signaling, was identified as the direct target gene of miR-1907. Taken together, miR-1907 accelerates hepatocyte proliferation during liver regeneration by activating autophagy; thus pharmacological intervention regulating miR-1907/autophagy axis may be therapeutically beneficial in liver transplantation and liver failure by inducing liver regeneration.
Highlights
Liver diseases are a major medical problem for health care systems worldwide [1, 2]
Alcoholism, persistent viral infection, and liver metabolic disorders are the fundamental reason for growing incidence of liver cancer and other liver diseases associated with high mortality [3, 4]
GSK3β overexpression attenuated miR-1907-induced autophagy activation in CCL9.1 cells (Figure 4(g)). These results demonstrate that partial hepatectomy (PH)-induced upregulation of miR-1907 accelerates hepatocyte proliferation and liver regeneration by inhibiting GSK3β and activation autophagy
Summary
Liver diseases are a major medical problem for health care systems worldwide [1, 2]. Alcoholism, persistent viral infection, and liver metabolic disorders are the fundamental reason for growing incidence of liver cancer and other liver diseases associated with high mortality [3, 4]. The underlying mechanisms of miRNAs in regulation of liver regeneration remain largely unclear. Autophagy functions as a survival mechanism during cellular stress and contributes to hepatocyte proliferation following PH. Modulating autophagy might be an effective method of promoting liver regeneration and ameliorating liver injury following PH [12]. Both miRNAs and autophagy are involved in liver regeneration, little is known about whether miRNAs regulate hepatocyte proliferation and liver growth by activating autophagy during PH. We carried out an expression analysis of miRNAs during liver regeneration in mice after PH and identified its mechanism of regulating liver regeneration.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
