银屑病皮损组织中PPIL6基因的下调表达与功能

Down-Regulation of PPIL6 Gene in Psoriatic Skin and Its Function

目的：分析人类脯氨酸异构酶基因PPIL6（ peptidylprolyl isomerase-like 6）在银屑病皮损组织中的表达异常，并研究PPIL6对信号通路及皮肤细胞增殖的影响。方法利用生物信息学方法从已经发表的基因芯片表达谱数据中分析脯氨酸异构酶（ PPIase）家族基因在银屑病皮损组织和正常皮肤中的表达差异。通过双荧光素酶报告系统研究PPIL6对Rb信号通路的影响。通过Western印迹研究PPIL6对Rb磷酸化的调控。通过染色质免疫沉淀（ ChIP）研究PPIL6敲降表达后E2 F1与下游基因EZH2启动子结合能力的变化。通过MTT实验检测PPIL6对人永生化表皮细胞HaCat增殖能力的影响。结果 PPIL6在银屑病皮损组织中下调表达， PPIL6过表达能够激活Rb信号通路，其机制可能是抑制Rb磷酸化。 PPIL6敲降表达上调E2 F1与EZH2启动子的结合。功能实验表明PPIL6过表达抑制HaCat细胞的增殖。结论 PPIL6可能在银屑病的发生发展过程中发挥重要作用。

Objective To analyze the abnormal expression of human peptidylprolyl isomerase-like 6 （ PPIL6） in psoriatic skin and its effects on signaling pathways and the proliferation of skin cells.Methods The difference in the expression of peptide-prolyl isomerases （ PPIase ） was ana-lyzed between psoriatic and normal skins based on published microarray data by using bioinformatic tools.The effect of PPIL6 on Rb signal pathway was evaluated by dual-luciferase assay.Regulation of PPIL6 on Rb phosphorylation was detected using Western blotting.The effect of PPIL6 knockdown on the binding of E2 F1 to the promoter of its downstream gene, EZH2, was monitored by ChIP as-say.The effect of PPIL6 on the proliferation of skin cell line HaCat was measured by MTT as-say.Results PPIL6 was downregulated in psoriatic skin tissues.Over-expressed PPIL6 could acti-vate Rb signal pathway via inhibition of Rb phosphorylation.PPIL6 knockdown increased the binding of E2 F1 to EZH2 promoter.Functional study showed that PPIL6 overexpression inhibited the prolif-eration of HaCat cells.Conclusion PPIL6 plays an important role in the initiation and development of psoriasis.