Deficiency in the LIM-only protein Fhl2 impairs skin wound healing

Wixler V, Hirner S, Müller JM, Gullotti L, Will C, Kirfel J, Günther T, Schneider H, Bosserhoff AK, Schorle H, Park JH, Schuele R, Büttner R (2007)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 2007

Journal

The Journal of Cell Biology Rockefeller University Press

Book Volume: 177

Pages Range: 163-172

Journal Issue: 1

DOI: 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 ́-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. © The Rockefeller University Press.

Authors with CRIS profile

Holm Schneider

Involved external institutions

Medizinische Universität Innsbruck AT Austria (AT) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Universität Regensburg DE Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) Universitätsklinikum Münster DE Germany (DE)

How to cite

APA:

Wixler, V., Hirner, S., Müller, J.M., Gullotti, L., Will, C., Kirfel, J.,... Büttner, R. (2007). Deficiency in the LIM-only protein Fhl2 impairs skin wound healing. The Journal of Cell Biology, 177(1), 163-172. https://doi.org/10.1083/jcb.200606043

MLA:

Wixler, Viktor, et al. "Deficiency in the LIM-only protein Fhl2 impairs skin wound healing." The Journal of Cell Biology 177.1 (2007): 163-172.

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