Placenta growth factor is induced in human keratinocytes during wound healing

Placenta growth factor (PlGF) is a dimeric glycoprotein, structurally and f unctionally related to the vascular endothelial growth factor, a potent ang iogenic/permeability factor known to play a role in the neoangiogenesis dur ing wound repair. In this study we evaluated the expression of PlGF in huma n keratinocytes and investigated its possible role in wound healing. Northe rn blot analysis on cultured keratinocytes revealed a 1.7 kb mRNA transcrip t and reverse transcriptase-polymerase chain reaction allowed the detection of two PlGF isoforms generated by alternative RNA splicing. PlGF and vascu lar endothelial growth factor homodimers as well as vascular endothelial gr owth factor/PlGF heterodimers could be detected in keratinocyte conditioned medium. Increased expression of both PlGF mRNA and protein was observed up on treatment of keratinocytes with epidermal growth factor, transforming gr owth factor-alpha, transforming growth factor-beta, and interleukin-6, all cytokines present at the wound site during the early phase of repair, The a nalysis of human full-thickness healing wounds revealed appreciable levels of PlGF mRNA and protein in the migrating keratinocytes starting from day 3 after injury, and increasing at day 5, At day 7 PlGF mRNA was no longer de tectable, while the protein was still expressed by migrating suprabasal ker atinocytes, At day 13, when the wound had reepithelialized, PlGF immunostai ning was completely negative. By in situ hybridization an intense signal fo r PlGF was also found on endothelial capillaries adjacent to the wound. The se data demonstrate that keratinocytes are a source of PlGF during wound he aling in vivo and indicate a role for this factor in the neoangiogenesis pr ocess associated with cutaneous wound repair.