Ia. Darby et al., Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA, LAB INV, 81(7), 2001, pp. 937-943
Sox18 encodes a member of the Sry-related high mobility group box (SOX) fam
ily of developmental transcription factors. Examination of Sox18 expression
during embryogenesis has shown that Sox18 is expressed transiently in endo
thelial cells of developing blood vessels, and mutations in Sox18 have been
found to underlie the mouse vascular and hair follicle mutant ragged. In t
his study we have examined the expression of Sox18 in angiogenesis during w
ound healing. Full-thickness skin wounds were created in mice, and subseque
nt expression of vascular endothelial growth factor (VEGF), the VEGF recept
or Flk-1, alpha1 (iv) collagen (Col4a1), and Sox18 were studied using in si
tu hybridization. As has been previously reported, VEGF was expressed predo
minantly in the keratinocytes at the wound margins. Sox18 expression was fo
und Rye days after wounding during capillary sprouting in granulation tissu
e and persisted through the proliferative phase of healing, but was not det
ected in fully epithelialized wounds 21 days after wounding. Sox18 mRNA exp
ression was detected in capillaries within the granulation tissue and showe
d an identical pattern of distribution to Flk-1 and Col4a1 mRNA expression
in endothelial cells. Immunostaining with a polyclonal anti-Sox18 antibody
showed SOX18 protein localized in capillary endothelial cells within the gr
anulation tissue. capillaries in the subcutaneous tissue of unwounded skin
showed no Sox18 expression. Sox18 may therefore represent a transcription f
actor involved in the induction of angiogenesis during wound healing and ti
ssue repair, but not in the maintenance of endothelial cells in undamaged t
issue.