| First Author | Rius-Pérez S | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 3775 |
| PubMed ID | 30846722 | Mgi Jnum | J:275634 |
| Mgi Id | MGI:6307724 | Doi | 10.1038/s41598-019-39428-3 |
| Citation | Rius-Perez S, et al. (2019) p38alpha deficiency restrains liver regeneration after partial hepatectomy triggering oxidative stress and liver injury. Sci Rep 9(1):3775 |
| abstractText | p38alpha MAPK negatively regulates the G1/S and G2/M cell cycle transitions. However, liver-specific p38alpha deficiency impairs cytokinesis and reduces hepatocyte proliferation during cirrhosis and aging in mice. In this work, we have studied how p38alpha down-regulation affects hepatocyte proliferation after partial hepatectomy, focusing on mitotic progression, cytokinesis and oxidative stress. We found that p38alpha deficiency triggered up-regulation of cyclins A1, B1, B2, and D1 under basal conditions and after hepatectomy. Moreover, p38alpha-deficient hepatocytes showed enhanced binucleation and increased levels of phospho-histone H3 but impaired phosphorylation of MNK1 after hepatectomy. The recovery of liver mass was transiently delayed in mice with p38alpha-deficient hepatocytes vs wild type mice. We also found that p38alpha deficiency caused glutathione oxidation in the liver, increased plasma aminotransferases and lactate dehydrogenase activities, and decreased plasma protein levels after hepatectomy. Interestingly, p38alpha silencing in isolated hepatocytes markedly decreased phospho-MNK1 levels, and silencing of either p38alpha or Mnk1 enhanced binucleation of hepatocytes in culture. In conclusion, p38alpha deficiency impairs mitotic progression in hepatocytes and restrains the recovery of liver mass after partial hepatectomy. Our results also indicate that p38alpha regulates cytokinesis by activating MNK1 and redox modulation. |
