Study On The Role Of PI3K/Akt Signal Transduction Pathway In The Psoriasis Vulgaris

Objectives To investigate the role of PI3K/Akt signal pathway in the pathogenesis of psoriasis vulgaris by measuring the expression of VEGF,Akt and survivin proteins in psoriasis vulgaris and the effect of VEGF on the expression survivin in HaCaT cells, and further analyse their relationships.Methods Paraffin-embedded tissue sections containing 30 psoriasis patients and 10 normal controls were analyzed by SP immunohisto-chemistry technique for the expression of VEGF, Akt and survivin, which was quantitated by image analysis in the context of histopathological parameters. PASI score of the psoriasis lesions are detected. The expressions of VEGF, Akt and survivin between patients with psoriasis were compared to that in normal controls. The relationship among the expression of VEGF, Akt and survivin was also analyzed. HaCaT cells are cultured with VEGF in escalating doses. A specific inhibitor of PI3-kinase, LY294002, is used to block Akt phosphorylation. RT-PCR is used to measure survivin mRNA expression.Results(1)The expression and distribution of VEGF, Akt and survivin was statistically significant higher in lesional epidermis than that in epidermis of the controls (P<0.05).(2)There was significantly positive correlation between the level of Akt and survivin expression in lesional epidermis and PASI score of patients (P<0.05), but there was no significantly correlation between the level of VEGF expression and PASI score of patients(P>0.05).(3)There was significantly positive correlation between the expression of VEGF and survivin, VEGF and Akt, Akt and survivin in lesional epidermis (P<0.05).(4)Stimulation of HaCaT cells with VEGF results in an increase in survivin protein expression in a dose-dependent fashion. Blockade of Akt phosphorylation with LY294002 abrogates the effects of VEGF upon survivin.Conclusions1) Through PI3K/Akt signal pathway the expression of survivin can be promoted by the high level expression of VEGF. This may play a critical role in the pathogenesis of psoriasis keratinocytes abnormal apoptosis.2) High level expression of Akt and surivivin may be associated with the degree of the severity of psoriasis.