中波紫外线通过抑制Hippo通路促进AKT磷酸化致日光性角化病发病机制研究

Ultraviolet B promotes the development of Actinic Keratosis through AKT phosphorylation by Hippo pathway inhibition

目的探究在HaCaT细胞和A431细胞中,中波紫外线(UVB)通过Hippo通路对AKT磷酸化的影响。方法检测日光性角化病(AK)和皮肤鳞状细胞癌(cSCC)中Yes相关蛋白(Yes-associated protein,YAP)、丝/苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)表达量。构建YAP表达量下降的HaCaT细胞和A431细胞,通过蛋白免疫印迹法分析照射UVB对YAP表达量下降的细胞Hippo通路和AKT磷酸化的影响。结果cSCC中YAP、AKT表达量均高于AK,AKT表达量与YAP正相关。UVB照射HaCaT细胞时,其中YAP表达量随照光剂量增加(P<0.01)。通过细胞转染使HaCaT细胞、A431细胞yap基因相对表达量下降,YAP表达量下降(PHaCaT<0.01,PA431<0.001)。UVB照射HaCaT细胞和A431细胞时,Hippo通路受抑制,促进AKT磷酸化。结论UVB照射通过抑制Hippo通路促进YAP表达,进而促进AKT磷酸化,提示这可能是AK转变为cSCC的发病机制之一。

Objective To investigate the effect of ultraviolet B(UVB)on AKT phosphorylation through the Hippo pathway in HaCaT cells and A431 cells.Methods To detect the expression levels of Yes-associated protein(YAP)and serine/threonine protein kinase(AKT)in actinic keratosis(AK)and skin squamous cell carcinoma(cSCC).HaCaT cells and A431 cells with decreased expression of YAP were constructed,and analyzed the effects of UVB irradiation on Hippo pathway and AKT phosphorylation of cells with decreased YAP expression by Western blotting.Results The expression levels of YAP and AKT in cSCC were higher than those in AK,and the expression level of AKT was positively correlated with YAP.When UVB irradiated HaCaT cells,the expression of YAP increased with the irradiation dose(P<0.01).The relative expression of the yap gene in HaCaT cells and A431 cells decreased by cell transfection,while the expression of yap decreased(PHaCaT<0.01,PA431<0.001).When UVB irradiated HaCaT cells and A431 cells,the Hippo pathway was inhibited,thus promoting AKT phosphorylation.Conclusion UVB irradiation promotes the expression of YAP and phosphorylation of AKT by inhibiting Hippo pathway,which suggests that this may be one of the pathogenesis of the transformation of AK into cSCC.