| First Author | Speicher T | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3862 | PubMed ID | 24844558 |
| Mgi Jnum | J:278219 | Mgi Id | MGI:6296191 |
| Doi | 10.1038/ncomms4862 | Citation | Speicher T, et al. (2014) Knockdown and knockout of beta1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling. Nat Commun 5:3862 |
| abstractText | The liver has a unique regenerative capability, which involves extensive remodelling of cell-cell and cell-matrix contacts. Here we study the role of integrins in mouse liver regeneration using Cre/loxP-mediated gene deletion or intravenous delivery of beta1-integrin siRNA formulated into nanoparticles that predominantly target hepatocytes. We show that although short-term loss of beta1-integrin has no obvious consequences for normal livers, partial hepatectomy leads to severe liver necrosis and reduced hepatocyte proliferation. Mechanistically, loss of beta1-integrin in hepatocytes impairs ligand-induced phosphorylation of the epidermal growth factor and hepatocyte growth factor receptors, thereby attenuating downstream receptor signalling in vitro and in vivo. These results identify a crucial role and novel mechanism of action of beta1-integrins in liver regeneration and demonstrate that protein depletion by nanoparticle-based delivery of specific siRNA is a powerful strategy to study gene function in the regenerating liver. |
