Activation of VEGFR-2 signaling in response to moderate dose of ultraviolet B promotes survival of normal human keratinocytes

摘要: Mounting evidence indicates that signaling via VEGF receptors (VEGFRs) extends beyond blood vessel formation. Recently, VEGFRs are also found to be constitutively expressed in keratinocytes and epidermal appendages. Here, we show the expression of (including VEGFR-1, VEGFR-2, NRP-1) was significantly enhanced by moderate dose ultraviolet B (UVB) normal human epidermis. The elevated UVB independent autocrine stimulation their natural ligand, VEGF, but mainly mediated through hypoxia oxidative stress. Moderate promoted tyrosine phosphorylation VEGFR-1 this effect again independent. Both α δ isoforms protein kinase C (PKC) were required for UVB-induced only isoform VEGFR-2 phosphorylation. or PKC completely inhibited PP2, a specific inhibitor Src family kinases (SFKs), indicating SFKs upstream VEGFRs. exerted an anti-apoptotic keratinocytes, whereas high played as inflammatory factor. Of note, neutralization not exacerbated cell death reduced survival keratinocytes. Furthermore, activation ERK1/2 Akt UVB, suggesting involved pro-survival mechanism PI3-K/Akt pathway. Taken together, demonstrate first time is activated promotes under irradiation.