利用基因芯片筛选与银屑病发病相关的GPCR家族基因

摘要

Objective In order to indicate the possible role for G-protein coupled receptors (GPCRs) in disease machanism at the genetic level and to discuss the possibility of inhibition of GPCRs as treatment for individules of psoriasis in the future.Methods Microarray expression profiling and reverse transcription polymerase chain reaction (RT-PCR) were used to characterize gene expressions that relate to GPCRs with more than two fold changes in psoriatic lesions and non-lesion skin from three plaque psoriasis patients.Results Six upregulated GPCR genes (CXCR6,GPR110,GPR171,CXCR2,PTARF and LPHN2) and eleven GPCR downregulated genes (GPR12,CHRM1,ADRB2,CHAM3,NPY 1R,ADRA 1B,GPR182,ADAR2A,LGR6,GPRC5C and F2R) were further validated by Microarray expression profiling and Realtime PCR.Of which,CXCR6 was demonstrated to be required for psoriasis development.Conclusion Gene expressions that relate to GPCRs in psoriatic lesions and non-lesion skin are closely related to the pathogenesis of psoriasis.%目的 从基因水平上探讨G蛋白耦联受体(GPCRs)在银屑病发病机制中的作用,讨论通过抑制GPCRs的方法治疗银屑病的可能性,为后期寻找银屑病的新的治疗靶点提供依据.方法 利用基因芯片检测技术和实时定量PCR的方法找出3例斑块型银屑病患者受累皮肤组织和非受累皮肤组织与GPCRs相关的大于2倍差异基因.结果 通过基因芯片技术和实时定量PCR验证得出6个上调基因(CXCR6,GPR 110,GPR171,CXCR2,PTARF,LPHN2)和11个下调基因(GPR12,CHRM1,ADRB2,CHAM3,NPY1R,ADRA1B,GPR182,ADAR2A,LGR6,GPRC5C,F2R).其中,CXCR6已被证实与银屑病的发病相关.结论 银屑病患者受累皮肤组织和非受累皮肤组织与GPCRs相关的差异表达基因与银屑病的发病机制密切相关,值得进一步深入探讨.