uPAR-deficient mouse keratinocytes fail to produce EGFR-dependent laminin-5, affecting migration in vivo and in vitro

Silvia d'Alessio, Laura Gerasi, Francesco Blasi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3922-3932
Number of pages11
JournalJournal of Cell Science
Volume121
Issue number23
DOIs
Publication statusPublished - Dec 1 2008

Fingerprint

Keratinocytes
Epidermal Growth Factor Receptor
Wound Healing
Epidermal Growth Factor
Knockout Mice
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Urokinase-Type Plasminogen Activator
Pathologic Processes
Epidermis
Tyrosine
Phosphorylation
In Vitro Techniques
kalinin
Inflammation
Phenotype
Growth
Neoplasms

Keywords

  • EGF-receptor
  • Keratinocytes
  • Laminin-5
  • uPAR
  • Wound healing

ASJC Scopus subject areas

  • Cell Biology

Cite this

uPAR-deficient mouse keratinocytes fail to produce EGFR-dependent laminin-5, affecting migration in vivo and in vitro. / d'Alessio, Silvia; Gerasi, Laura; Blasi, Francesco.

In: Journal of Cell Science, Vol. 121, No. 23, 01.12.2008, p. 3922-3932.

Research output: Contribution to journalArticle

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