Hox D3 expression in normal and impaired wound healing.
BACKGROUND
We have previously shown that Hox D3 and Hox B3 can promote angiogenesis. As angiogenesis is essential for wound healing, we examined expression of these genes in the vasculature following wounding in normal and genetically diabetic adult mice with impaired healing.


METHODS
In situ hybridization was performed on tissues taken 0, 1, 4, 7, and 14 days following administration of linear wounds in wild-type and genetically diabetic mice. Expression of Hox D3 and Hox B3, angiogenesis, and synthesis of type I collagen were assessed in the wound.


RESULTS
Hox B3 was expressed in endothelial cells (ECs) of both medium and small vessels in unwounded tissue, whereas little Hox D3 was detected in resting ECs. Hox D3 expression was significantly upregulated by 1 day after wounding in ECs of vessels immediately adjacent to the wound site, and expression was maintained for at least 7 days. In the diabetic mice, expression of Hox B3 was similar to that of wild-type mice. In contrast, expression of Hox D3 in ECs was significantly lower and delayed during wound repair in diabetic mice. In cultured microvascular ECs, Hox D3 selectively induced high levels of collagen I mRNA expression. Hox D3-deficient wounds of diabetic animals also displayed a reduction in expression and deposition of type I collagen.


CONCLUSIONS
These results suggest that reduced angiogenesis and type I collagen in diabetic mice with impaired wound healing may be related to deficient Hox D3 expression, and restoring Hox D3 expression may enhance angiogenesis and wound repair.
Uyeno
L A
LA
Surgical Research Laboratory, University of California, San Francisco, San Francisco, California 94143, USA.
Newman-Keagle
J A
JA
Cheung
I
I
Hunt
T K
TK
Young
D M
DM
Boudreau
N
N
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D004268:DNA-Binding Proteins; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014945:Wound Healing / Q000502:physiology*; D029867:Xenopus Proteins
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C078105:Hox 2.7 protein, Xenopus; C484113:Hoxd3 protein, mouse; D012333:RNA, Messenger; D029867:Xenopus Proteins; D003094:Collagen