| First Author | Krampert M | Year | 2008 |
| Journal | Lab Invest | Volume | 88 |
| Issue | 11 | Pages | 1204-14 |
| PubMed ID | 18762776 | Mgi Jnum | J:141182 |
| Mgi Id | MGI:3817380 | Doi | 10.1038/labinvest.2008.81 |
| Citation | Krampert M, et al. (2008) A gain-of-function mutation in the PDGFR-beta alters the kinetics of injury response in liver and skin. Lab Invest 88(11):1204-14 |
| abstractText | Platelet-derived growth factor (PDGF) isoforms stimulate cell proliferation, migration and survival. We recently generated mice carrying a gain-of-function mutation within the activation loop of PDGF beta-receptor (PDGFR-beta D849N). Embryonic fibroblasts derived from these mice show elevated basal phosphorylation and altered kinetics for ligand-induced activation of PDGFR-beta, as well as enhanced proliferation and migration. To investigate the effect of this mutation in vivo, we used carbon tetrachloride-induced liver injury as a model system. We observed a higher basal activation of mutant PDGFR-beta in unchallenged livers; however, the difference in activation upon carbon tetrachloride stimulation was lower than expected, an effect that might be explained by a delayed response of the mutated receptor toward reactive oxygen species. Mutant mice showed enhanced proliferation of nonparenchymal liver cells and activation of hepatic stellate cells, leading to a small increase in early fibrosis formation. Another mouse strain lacking the binding site for phosphatidylinositol-3' kinase in PDGFR-beta showed the reverse phenotype. These results suggest an important role for PDGFR-beta signaling in the early injury-response. We confirmed this hypothesis with a second injury model, cutaneous wound healing, where we observed earlier proliferation and formation of granulation tissue in D849N-mutant mice. |
