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Modulation of Scar Formation by Vascular Endothelial Growth Factor
Author(s) -
Wilgus T.A.,
Oberyszyn T.M.,
Bergdall V.K.,
Ferreira A.F.,
DiPietro L.A.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130215bf.x
Subject(s) - angiogenesis , cd31 , vascularity , vascular endothelial growth factor , wound healing , scars , fetus , medicine , pathology , inflammation , neovascularization , immunohistochemistry , blood vessel , pathological , vegf receptors , immunology , biology , pregnancy , genetics
Several lines of evidence demonstrate that limited inflammation is key for scarless healing to take place in early fetal skin. Because inflammation and angiogenesis are often linked in pathological processes, we hypothesized that angiogenesis may play a significant role in the regulation of scar formation. A mouse model of fetal wound repair was utilized to study angiogenesis in wounds generated at either embryonic day 15 (E15), when scarless healing takes place, or embryonic day 18 (E18), when significant scarring occurs. CD31 immunohistochemical staining and image analysis were used to calculate blood vessel density at 7 days post‐wounding. Wounds generated at E15 showed no increase in vessel density above levels found in unwounded, age‐matched skin. In contrast, wounds generated at E18 displayed a 45% increase in vessel density compared to control skin, similar to what is seen during adult wound healing. Increased protein levels of vascular endothelial growth factor (VEGF) in 3 day wounds generated at E18 (8.06 ± 1.89 pg VEGF/μg protein compared to 1.99 ± 0.4 in wounds made at E15) likely contribute to the increase in vascularity. In addition, injection of E15 wounds with 0.05 μg of VEGF resulted in the production of a scar, compared to control wounds which healed without a scar. To further explore the idea that VEGF may contribute to scarring, we examined the effects of VEGF neutralization on scar formation in adult murine skin. Anti‐VEGF antibody injections resulted in a significant reduction in scar formation compared to control scars based on histological and ultrastructural analysis. Our studies suggest a novel role for VEGF in promoting scar tissue deposition, and suggest that VEGF inhibitors may be useful for limiting cutaneous fibrosis.