title: Peroxiredoxin 6 is required for blood vessel integrity in wounded skin.
abstract: Peroxiredoxin 6 (Prdx6) is a cytoprotective enzyme with largely unknown in vivo functions. Here, we use Prdx6 knockout mice to determine its role in UV protection and wound healing. UV-mediated keratinocyte apoptosis is enhanced in Prdx6-deficient mice. Upon skin injury, we observe a severe hemorrhage in the granulation tissue of knockout animals, which correlates with the extent of oxidative stress. At the ultrastructural level endothelial cells appear highly damaged, and their rate of apoptosis is enhanced. Knock-down of Prdx6 in cultured endothelial cells also increases their susceptibility to oxidative stress, thus confirming the sensitivity of this cell type to loss of Prdx6. Wound healing studies in bone marrow chimeric mice demonstrate that Prdx6-deficient inflammatory and endothelial cells contribute to the hemorrhage phenotype. These results provide insight into the cross-talk between hematopoietic and resident cells at the wound site and the role of reactive oxygen species in this interplay.
authors.affiliation: Institute of Cell Biology, Department of Biology, ETH Zurich, Honggerberg, CH-8093 Zurich, Switzerland.
authors.forename: Angelika
authors.initials: A
authors.lastname: Kümin
authors.forename: Matthias
authors.initials: M
authors.lastname: Schäfer
authors.forename: Nikolas
authors.initials: N
authors.lastname: Epp
authors.forename: Philippe
authors.initials: P
authors.lastname: Bugnon
authors.forename: Christiane
authors.initials: C
authors.lastname: Born-Berclaz
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.forename: Anke
authors.initials: A
authors.lastname: Klippel
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006470:Hemorrhage / Q000209:etiology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000201:enzymology / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000293:injuries*; D014466:Ultraviolet Rays; D014471:Umbilical Veins / Q000166:cytology; D014916:Whole-Body Irradiation; D014945:Wound Healing / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse