RT Journal Article
SR Electronic
T1 Selective Deficiency of HIF-1α in Myeloid Cells Influences Secondary Intention Wound Healing in Mouse Skin
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 879
OP 884
VO 23
IS 6
A1 RICHARD A. OWINGS
A1 MARJAN BOERMA
A1 JUNRU WANG
A1 MAAIKE BERBEE
A1 KEITH R. LADEROUTE
A1 LEE S.F. SODERBERG
A1 EMRE VURAL
A1 MARTIN HAUER JENSEN
YR 2009
UL http://iv.iiarjournals.org/content/23/6/879.abstract
AB Background: Hypoxia-inducible factor-1 (HIF-1) influences myeloid cell function. In this study we examined the role of myeloid cell HIF-1α on wound healing in vivo using a cell-specific knockout (KO) mouse model. Materials and Methods: HIF-1α KO mice and wild-type (WT) controls received 8 mm full thickness dorsal dermal wounds. Wound dimensions were measured until full closure. Tissue was obtained from 3-day-old wounds for (immuno-)histochemical analysis. Production of interleukin-1β (IL-1β) and nitric oxide (NO) in response to lipopolysaccharide (LPS) and/or desferrioxamine (DFX) was examined in vitro. Results: Early wound closure occurred significantly faster in HIF-1α KO mice than in WT mice. Wounds of KO mice contained similar numbers of neutrophils and macrophages, but more activated keratinocytes, consistent with accelerated re-epithelialization. Interestingly, while LPS and LPS+DFX elicited a similar IL-1β response in macrophages from the 2 mouse types, NO production was blunted in HIF-1α KO macrophages. Conclusion: Absence of HIF-1α in myeloid cells accelerates the early phase of secondary intention wound healing in vivo. This may be associated with a deficient ability of myeloid cells to initiate an appropriate NO production response. Pharmacologic modulators of HIF-1α should be explored in situations with abnormal wound healing.