title: Deficiency in the LIM-only protein Fhl2 impairs skin wound healing.
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 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.
authors.affiliation: Institute of Molecular Virology, Münster University Hospital Medical School, D-48149 Münster, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Wixler
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hirner
authors.forename: Judith M
authors.initials: JM
authors.lastname: Müller
authors.forename: Lucia
authors.initials: L
authors.lastname: Gullotti
authors.forename: Carola
authors.initials: C
authors.lastname: Will
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
authors.forename: Thomas
authors.initials: T
authors.lastname: Günther
authors.forename: Holm
authors.initials: H
authors.lastname: Schneider
authors.forename: Anja
authors.initials: A
authors.lastname: Bosserhoff
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
authors.forename: Jung
authors.initials: J
authors.lastname: Park
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D012879:Skin Physiological Phenomena; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; D050719:Crk-Associated Substrate Protein; C491382:Fhl2 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D003094:Collagen