| First Author | D'Alessio S | Year | 2008 |
| Journal | J Cell Sci | Volume | 121 |
| Issue | Pt 23 | Pages | 3922-32 |
| PubMed ID | 19001498 | Mgi Jnum | J:145893 |
| Mgi Id | MGI:3836241 | Doi | 10.1242/jcs.037549 |
| Citation | D'Alessio S, et al. (2008) uPAR-deficient mouse keratinocytes fail to produce EGFR-dependent laminin-5, affecting migration in vivo and in vitro. J Cell Sci 121(Pt 23):3922-32 |
| abstractText | The urokinase receptor (uPAR) is involved in a series of pathological processes, from inflammation to cancer. We have analyzed in detail the role of uPAR and the mechanisms involved in keratinocyte behavior during wound healing by exploiting uPAR-knockout (KO) mice. In vivo, uPAR-KO mice showed delayed wound healing, with abnormal keratinocyte migration and proliferation. In vitro, unlike wild-type cells, primary uPAR-KO keratinocytes did not proliferate in response to epidermal growth factor (EGF), their growth and migration were not inhibited by EGF-receptor (EGFR) inhibitors, and they did not adhere to uncoated surfaces. Whereas EGFR levels in uPAR-KO keratinocytes were normal, there was no tyrosine phosphorylation upon addition of EGF, and its downstream targets, extracellular-signal-regulated kinases 1 and 2 (ERK1/2), were not activated. Re-introduction of mouse uPAR rescued all phenotypes. In vitro adhesion and migration defects were associated with the failure of uPAR-KO keratinocytes to normally produce and secrete laminin-5 (LN5), an event that requires EGFR signaling. These results were confirmed in vivo, with LN5 being upregulated during wound healing in wild-type but not in uPAR-KO epidermis. |
