Peroxiredoxin 6 is required for blood vessel integrity in wounded skin.
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.
Kümin
Angelika
A
Institute of Cell Biology, Department of Biology, ETH Zurich, Honggerberg, CH-8093 Zurich, Switzerland.
Schäfer
Matthias
M
Epp
Nikolas
N
Bugnon
Philippe
P
Born-Berclaz
Christiane
C
Oxenius
Annette
A
Klippel
Anke
A
Bloch
Wilhelm
W
Werner
Sabine
S
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
D017382:Reactive Oxygen Species; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse