title: Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF).
abstract: Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing.
authors.affiliation: Department of Physiology, University of Alcala, Alcalá de Henares, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Serrano
authors.forename: Maria L
authors.initials: ML
authors.lastname: Díez-Marqués
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Puyol
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Herrero-Fresneda
authors.forename: Del Moral
authors.initials: del M
authors.lastname: Raimundo García
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: Maria P
authors.initials: MP
authors.lastname: Ruiz-Torres
authors.forename: Diego
authors.initials: D
authors.lastname: Rodríguez-Puyol
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*; D000099200:Scaffold Protein ILK
chemical_list: D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK