Deficiency in the LIM-only protein Fhl2 impairs skin wound healing.
J Cell Biol
; 177(1): 163-72, 2007 Apr 09.
Article
en En
| MEDLINE
| ID: mdl-17420295
ABSTRACT
After skin wounding, the repair process is initiated by the release of growth factors, cytokines, and bioactive lipids from injured vessels and coagulated platelets. These signal molecules induce synthesis and deposition of a provisional extracellular matrix, as well as fibroblast invasion into and contraction of the wounded area. We previously showed that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of the LIM-only protein Fhl2 in response to activation of the RhoA GTPase (Muller, J.M., U. Isele, E. Metzger, A. Rempel, M. Moser, A. Pscherer, T. Breyer, C. Holubarsch, R. Buettner, and R. Schule. 2000. EMBO J. 19359-369; Muller, J.M., E. Metzger, H. Greschik, A.K. Bosserhoff, L. Mercep, R. Buettner, and R. Schule. 2002. EMBO J. 21736-748.). We demonstrate impaired cutaneous wound healing in Fhl2-deficient mice rescued by transgenic expression of Fhl2. Furthermore, collagen contraction and cell migration are severely impaired in Fhl2-deficient cells. Consequently, we show that the expression of alpha-smooth muscle actin, which is regulated by Fhl2, is reduced and delayed in wounds of Fhl2-deficient mice and that the expression of p130Cas, which is essential for cell migration, is reduced in Fhl2-deficient cells. In summary, our data demonstrate a function of Fhl2 as a lipid-triggered signaling molecule in mesenchymal cells regulating their migration and contraction during cutaneous wound healing.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fenómenos Fisiológicos de la Piel
/
Factores de Transcripción
/
Cicatrización de Heridas
/
Proteínas de Homeodominio
/
Proteínas Musculares
Límite:
Animals
Idioma:
En
Revista:
J Cell Biol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Alemania