c-Met is essential for wound healing in the skin

被引:262
作者
Chmielowiec, Jolanta
Borowiak, Malgorzata
Morkel, Markus
Stradal, Theresia
Munz, Barbara
Werner, Sabine
Wehland, Juergen
Birchmeier, Carmen
Birchmeier, Walter [1 ]
机构
[1] Max Delbruck Ctr Mol Med, Dept Canc Biol, D-13125 Berlin, Germany
[2] Max Delbruck Ctr Mol Med, Dept Neurosci, D-13125 Berlin, Germany
[3] Helmholtz Ctr Infect Res, Dept Cell Biol, D-38124 Braunschweig, Germany
[4] Charite Med Univ Berlin, Inst Physiol, D-14195 Berlin, Germany
[5] ETH Honggerberg, Inst Cell Biol, CH-8093 Zurich, Switzerland
关键词
D O I
10.1083/jcb.200701086
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:151 / 162
页数:12
相关论文
共 71 条
[1]  
Amendt C, 2002, J CELL SCI, V115, P2189
[2]   Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response [J].
Ashcroft, GS ;
Yang, X ;
Glick, AB ;
Weinstein, M ;
Letterio, JJ ;
Mizel, DE ;
Anzano, M ;
Greenwell-Wild, T ;
Wahl, SM ;
Deng, CX ;
Roberts, AB .
NATURE CELL BIOLOGY, 1999, 1 (05) :260-266
[3]   Diverse and potent activities of HGF/SF in skin wound repair [J].
Bevan, D ;
Gherardi, E ;
Fan, TP ;
Edwards, D ;
Warn, R .
JOURNAL OF PATHOLOGY, 2004, 203 (03) :831-838
[4]   Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase [J].
Birchmeier, C ;
Gherardi, E .
TRENDS IN CELL BIOLOGY, 1998, 8 (10) :404-410
[5]   Met, metastasis, motility and more [J].
Birchmeier, C ;
Birchmeier, W ;
Gherardi, E ;
Vande Woude, GF .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (12) :915-925
[6]   ESSENTIAL ROLE FOR THE C-MET RECEPTOR IN THE MIGRATION OF MYOGENIC PRECURSOR CELLS INTO THE LIMB BUD [J].
BLADT, F ;
RIETHMACHER, D ;
ISENMANN, S ;
AGUZZI, A ;
BIRCHMEIER, C .
NATURE, 1995, 376 (6543) :768-771
[7]   Met provides essential signals for liver regeneration [J].
Borowiak, M ;
Garratt, AN ;
Wüstefeld, T ;
Strehle, M ;
Trautwein, C ;
Birchmeier, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (29) :10608-10613
[8]   IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT [J].
BOTTARO, DP ;
RUBIN, JS ;
FALETTO, DL ;
CHAN, AML ;
KMIECIK, TE ;
VANDEWOUDE, GF ;
AARONSON, SA .
SCIENCE, 1991, 251 (4995) :802-804
[9]  
BYRNE C, 1994, DEVELOPMENT, V120, P2369
[10]  
Caldelari R, 2000, J INVEST DERMATOL, V114, P1064, DOI 10.1046/j.1523-1747.2000.00960-4.x