c-Met is essential for wound healing in the skin.
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.
Chmielowiec
Jolanta
J
Department of Cancer Biology, Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.
Borowiak
Malgorzata
M
Morkel
Markus
M
Stradal
Theresia
T
Munz
Barbara
B
Werner
Sabine
S
Wehland
Jürgen
J
Birchmeier
Carmen
C
Birchmeier
Walter
W
D000818:Animals; D019898:Autocrine Communication; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C045073:Cre recombinase; D019426:Integrases