Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
Open Access
- 9 April 2007
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 177 (1), 163-172
- https://doi.org/10.1083/jcb.200606043
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. 19:359–369; Muller, J.M., E. Metzger, H. Greschik, A.K. Bosserhoff, L. Mercep, R. Buettner, and R. Schule. 2002. EMBO J. 21:736–748.). 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 α-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.Keywords
This publication has 31 references indexed in Scilit:
- Four and Half Lim Protein 2 (FHL2) Stimulates Osteoblast DifferentiationJournal of Bone and Mineral Research, 2006
- FHL2 inhibits the activated osteoclast in a TRAF6-dependent mannerJCI Insight, 2005
- Focal adhesion kinase: in command and control of cell motilityNature Reviews Molecular Cell Biology, 2005
- Transgene-activated mesenchymal cells for articular cartilage repair: a comparison of primary bone marrow-, perichondrium/periosteum- and fat-derived cellsThe Journal of Gene Medicine, 2005
- The interplay between Src and integrins in normal and tumor biologyOncogene, 2004
- Extracellular Signal-Regulated Kinase 2 Interacts with and Is Negatively Regulated by the LIM-Only Protein FHL2 in CardiomyocytesMolecular and Cellular Biology, 2004
- Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodelingThrombosis and Haemostasis, 2003
- Lysophosphatidic Acid Enhances Collagen Gel Contraction by Hepatic Stellate Cells: Association with Rho-KinaseBiochemical and Biophysical Research Communications, 2000
- In Vitro System for Differentiating Pluripotent Neural Crest Cells into Smooth Muscle CellsPublished by Elsevier BV ,1998
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995