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Published online
doi:10.1083/jcb.200701086
The Journal of Cell Biology, Vol. 177, No. 1, 151-162
The Rockefeller University Press, 0021-9525 $30.00
© Chmielowiec et al.
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Article

c-Met is essential for wound healing in the skin



Jolanta Chmielowiec1, Malgorzata Borowiak2, Markus Morkel1, Theresia Stradal3, Barbara Munz4, Sabine Werner5, Jürgen Wehland3, Carmen Birchmeier2, and Walter Birchmeier1

1 Department of Cancer Biology and 2 Department of Neuroscience, Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany
3 Department of Cell Biology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany
4 Institute of Physiology, Charité-Medical University Berlin, 14195 Berlin, Germany
5 Institute of Cell Biology, ETH Zürich, Hönggerberg, CH-8093 Zürich, Switzerland

Correspondence to Walter Birchmeier: wbirch{at}mdc-berlin.de

Wound healing of the skin is a crucial regenerative process in adult mammals. We examined wound healing in conditional mutant mice, in which the c-Met gene that encodes the receptor of hepatocyte growth factor/scatter factor was mutated in the epidermis by cre recombinase. c-Met–deficient keratinocytes were unable to contribute to the reepithelialization of skin wounds. In conditional c-Met mutant mice, wound closure was slightly attenuated, but occurred exclusively by a few (5%) keratinocytes that had escaped recombination. This demonstrates that the wound process selected and amplified residual cells that express a functional c-Met receptor. We also cultured primary keratinocytes from the skin of conditional c-Met mutant mice and examined them in scratch wound assays. Again, closure of scratch wounds occurred by the few remaining c-Met–positive cells. Our data show that c-Met signaling not only controls cell growth and migration during embryogenesis but is also essential for the generation of the hyperproliferative epithelium in skin wounds, and thus for a fundamental regenerative process in the adult.

M. Morkel's present address is Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany.

Abbreviations used in this paper: E, embryonic day; HE, hyperproliferative epithelium; HGF/SF, hepatocyte growth factor/scatter factor; KGF, keratinocyte growth factor; P, postnatal day.


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