Role Of Histone Demethylase JMJD2D In Mice Liver Regeneration

Histone demmethylase JMJD2D(also known as KDM4D)is a member of the JMJD2(KDM4)protein family,compared with other members,the JMJD2D structure is unique,only JmjC domain and JmjN domain,not including PHD domain and Tudor domain.In general,JMJD2D can demethylate H3K9me3 and H3K9me2 to activate the expression of the target genes.As the largest glandular organ in the human body,the liver plays an extremely important role.When the liver is damaged,it can make use of the strong regeneration ability to compensate for the reduced volume and impaired function of the liver.This study mainly explored the mechanism of JMJD2D in liver regeneration of mice.In this study,we established a mice liver regeneration model by 2/3 partial hepatectomy(PHx),and we obtained the liver/body weight ratio at different time points after the PHx,the results showed that the liver/body weight ratio of JMJD2D-/-mice was significantly lower than that of wild-type mice;Meanwhile,Ki67 and BrdU staining showed that deficiency of JMJD2D might inhibit the proliferation of hepatocytes during liver regeneration in mice.Further experiments indicated that the expression of transcription factor FOXM1 and its target genes were significantly downregulated in JMJD2D-/-mice liver after PHx,such as CCNA2,CDK1,PLK1.In addition,knockdown JMJD2D in Hepl-6 cells inhibited the proliferation of Hep 1-6 cells,and the expression of FOXM1 and its target genes was also significantly downregulated.Additional,deficiency of JMJD2D did not affect the recruitment of macrophages or the IL-6/STAT3 signaling pathway during liver regeneration in mice after PHx.In conclusion,we speculated that deficiency of JMJD2D will downregulate the expression of FOXM1 and its target genes,which will inhibit the proliferation of hepatocyte in mice liver regeneration after PHx.This study has fundamental significance in improving the quality of patients after hepatectomy.