Role of DNAJB6 gene in the regeneration of liver resection and partial liver transplantation / 中华器官移植杂志

ABSTRACT

Objective:To explore the role and molecular mechanism of DNAJB6 in liver regeneration during partial liver transplantation(PLT).Methods:Dark agouti(DA, donor)and Lewis(recipient)rats were prepared for liver regeneration model of PLT.Rats were divided into before perfusion, after split liver perfusion, after portal vein opening, before abdominal closure and Day 3/7 after surgery groups(n=6 each)for timepoints of PLT.C57 mice were performed for residual liver regeneration model of partial hepatectomy and divided into control, Day 1/2/3/4/5 groups(n=6 each)for timepoints of hepatectomy.Gene Expression Omnibus liver regeneration data were utilized for locating DNAJB6 in liver regeneration.DNAJB6 low-expression human hepatocytes were constructed by DNAJB6-Si transfection.The relationship between DNAJB6 and liver regeneration was examined by Western blot detection of cell proliferation markers PCNA and CCK8 cell proliferation experiments.And the possible molecular mechanism of DNAJB6 regulating liver regeneration in PLT was studied by Western blot detection of nuclear protein and protein in cell proliferation signal pathway.Results:The result of residual liver regeneration of partial hepatectomy showed that DNAJ family genes were differentially expressed on regenerated liver gene chip and DNAJB6 was lowly expressed on regenerated liver gene chip.Meanwhile, DNAJB6 was lowly expressed in regenerated liver tissues of PLT and partial liver resection.After silencing DNAJB6 by transfecting DNAJB6-Si, the cellular expression level of PCNA and proliferation rate increased.However, nuclear extraction failed to detect the nuclear/plasma changes of β-catenin and the level of Wnt4 protein had no obvious change.Although the activation levels of p38 and JNK2 downstream of Ras/MAPK showed no change, there was a higher activation level of ERK.Conclusions:In regenerating liver tissue, hepatocytes may suppress the Ras/MEK/ERK signaling pathway by lowering the expression level of DNAJB6 to promote liver regeneration.