| First Author | Tormos AM | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 2 | Pages | e0171738 |
| PubMed ID | 28166285 | Mgi Jnum | J:247147 |
| Mgi Id | MGI:5918499 | Doi | 10.1371/journal.pone.0171738 |
| Citation | Tormos AM, et al. (2017) p38alpha regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging. PLoS One 12(2):e0171738 |
| abstractText | BACKGROUND: Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38alpha MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. METHODS: Wild type and p38alpha liver-specific knock out mice at different ages (after weaning, adults and old) were used. RESULTS: We show that p38alpha MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38alpha knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38alpha knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38alpha deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38alpha MAPK knock out mice exhibited reduced F-actin polymerization and a dramatic loss of actin cytoskeleton. This was associated with abnormal hyperactivation of RhoA and Cdc42 GTPases. Long-term p38alpha deficiency drives to inactivation of HSP27, which seems to account for the impairment in actin cytoskeleton as Hsp27-silencing decreased the number and length of actin filaments in isolated hepatocytes. CONCLUSIONS: p38alpha MAPK is essential for actin dynamics with age in hepatocytes. |
