Placenta growth factor (P1GF) is a dimeric glycoprotein, structurally and functionally related to the vascular endothelial growth factor, a potent angiogenic/permeability factor known to play a role in the neoangiogenesis during wound repair. In this study we evaluated the expression of PIGF in human keratinocytes and investigated its possible role in wound heating. Northern blot analysis on cultured keratinocytes revealed a 1.7 kb mRNA transcript and reverse transcriptase-polymerase chain reaction allowed the detection of two P1GF isoforms generated by alternative RNA splicing. P1GF and vascular endothelial growth factor homodimers as well as vascular endothelial growth factor/P1GF heterodimers could be detected in keratinocyte conditioned medium. Increased expression of both PIGF mRNA and protein was observed upon treatment of keratinocytes with epldermal growth factor, transforming growth factor-α, transforming growth factor-β, and interleukin-6, all cytokines present at the wound site during the early phase of repair. The analysis of human full-thickness healing wounds revealed appreciable levels of P1GF mRNA and protein in the migrating keratinocytes staring from day 3 after injury, and increasing at day 5. At day 7 P1GF mRNA was no longer detectable, while the protein was still expressed by migrating suprabasal keratinocytes. At day 13, when the wound had reepithelialized, P1GF immunostaining was completely negative. By in situ hybridization an intense signal for P1GF was also found on endothelial capillaries adjacent to the wound. These data demonstrate that keratinocytes are a source of P1GF during wound healing in vivo and indicate a role for this factor in the neoangiogenesis process associated with cutaneous wound repair.
- Wound healing
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