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

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...

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Autores principales: Wixler, Viktor, Hirner, Stephanie, Müller, Judith M., Gullotti, Lucia, Will, Carola, Kirfel, Jutta, Günther, Thomas, Schneider, Holm, Bosserhoff, Anja, Schorle, Hubert, Park, Jung, Schüle, Roland, Buettner, Reinhard
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064120/
https://www.ncbi.nlm.nih.gov/pubmed/17420295
http://dx.doi.org/10.1083/jcb.200606043
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author Wixler, Viktor
Hirner, Stephanie
Müller, Judith M.
Gullotti, Lucia
Will, Carola
Kirfel, Jutta
Günther, Thomas
Schneider, Holm
Bosserhoff, Anja
Schorle, Hubert
Park, Jung
Schüle, Roland
Buettner, Reinhard
author_facet Wixler, Viktor
Hirner, Stephanie
Müller, Judith M.
Gullotti, Lucia
Will, Carola
Kirfel, Jutta
Günther, Thomas
Schneider, Holm
Bosserhoff, Anja
Schorle, Hubert
Park, Jung
Schüle, Roland
Buettner, Reinhard
author_sort Wixler, Viktor
collection PubMed
description 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.
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spelling pubmed-20641202007-11-29 Deficiency in the LIM-only protein Fhl2 impairs skin wound healing Wixler, Viktor Hirner, Stephanie Müller, Judith M. Gullotti, Lucia Will, Carola Kirfel, Jutta Günther, Thomas Schneider, Holm Bosserhoff, Anja Schorle, Hubert Park, Jung Schüle, Roland Buettner, Reinhard J Cell Biol Research Articles 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. The Rockefeller University Press 2007-04-09 /pmc/articles/PMC2064120/ /pubmed/17420295 http://dx.doi.org/10.1083/jcb.200606043 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Wixler, Viktor
Hirner, Stephanie
Müller, Judith M.
Gullotti, Lucia
Will, Carola
Kirfel, Jutta
Günther, Thomas
Schneider, Holm
Bosserhoff, Anja
Schorle, Hubert
Park, Jung
Schüle, Roland
Buettner, Reinhard
Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
title Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
title_full Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
title_fullStr Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
title_full_unstemmed Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
title_short Deficiency in the LIM-only protein Fhl2 impairs skin wound healing
title_sort deficiency in the lim-only protein fhl2 impairs skin wound healing
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064120/
https://www.ncbi.nlm.nih.gov/pubmed/17420295
http://dx.doi.org/10.1083/jcb.200606043
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