Increase polyploid hepatocytes in HDAC6KO mice during liver regeneration

초록

[Purpose] Liver regeneration is an essential component of reparative process following liver injury and surgical resection which is a very complex process. The process is associated with a group of genetic and epigenetic factors. A variety of genetic regulations of liver regeneration have been reported, while few investigations have focused on its epigenetic control. We reported here the functional importance of histone deacetylase 6 (HDAC6) activities during mouse liver regeneration using mouse partial hepatectomy (PH). [Methods] PH was performed on WT and HDAC6 KO mice to detect hepatocyte proliferation during liver regeneration. The mice were sacrificed, and their liver tissues were harvested at sequential time points including 1, 2, 3, and 8 days postoperation. Liver regeneration was assessed by different tests such as FACS analysis of DNA contents of hepatocyte nuclei, counting cells undergoing mitosis, and DNA synthesis via a BrdU incorporation assay. [Results] Following PH, FACS analysis revealed the decrease of diploid hepatocytes to induce more polyploid hepatocytes in HDAC6 KO group by day 8 after PH. Mitotic failures were found in HDAC6 KO group by day 2 after PH when hepatocytes reached the peak of mitosis. BrdU incorporation assay showed the impairment of hepatocyte proliferation in HDAC6 KO mice during liver regeneration. [Conclusion] Our findings indicate that inhibiting HDAC6 activities delays mouse liver regeneration posthepatectomy relating to fail cytokinesis and increase polyploidy hepatocytes. The present results highlight a new role for HDAC6 in the process of liver regeneration.