RUNX家族在寻常型银屑病皮损中的表达

 目的 探究Runt相关转录因子（RUNX）家族在寻常型银屑病（PV）皮损中的表达和分布,并分析其水平与皮损中增殖、凋亡、免疫信号通路的相关性。方法 通过基因芯片分析14例健康人皮肤（HC）和17例PV患者皮损中RUNX1、2、3的转录水平,免疫组化分析11例HC、11例慢性湿疹（CE）和12例PV患者皮损中RUNX1、2、3的蛋白水平和分布,利用R语言分析基因芯片中RUNX与其他基因的相关性,并进行GO富集分析。结果 转录水平上,相比HC,PV皮损中RUNX1下调（HC：0.61±0.06,PV：0.54±0.02,P<0.01）、RUNX3上调（HC：0.77±0.04,PV：0.84±0.05,P<0.01）,而RUNX2的表达无差异（HC：0.78±0.05,PV：0.82±0.04,P=0.18）。免疫组化提示皮肤中RUNX1在表皮和真皮浸润炎症细胞中均有表达,而RUNX2、RUNX3则在炎症细胞上更为富集。相比HC,CE和PV表皮中RUNX1蛋白水平下调（HC：0.24±0.06,PV：0.11±0.02,CE：0.11±0.02,HC vs PV：P＜0.01,HC vs CE：P＜0.01）,PV表皮的RUNX2较HC、CE升高（HC：0.02±0.01,PV：0.04±0.02,CE：0.02±0.02,HC vs PV：P=0.018,PV vs CE：P=0.019）,RUNX3在三组间无差异（HC：0.005±0.004,PV：0.011±0.016,CE：0.015±0.20,P=0.861）。相关性和功能分析提示PV中RUNX1与增殖凋亡分子（BCL2A1、WNT2、WNT7B、WNT8A、WNT9B）相关,与Th17相关细胞因子（IL-17A、IL-17F、IL-17E）相关。与RUNX3呈正相关的基因主要富集在T细胞、淋巴细胞的活化和分化等通路,负相关的基因参与负调节WNT通路。RUNX3与Th1（STAT4、CXCR3、TNF）、Th17（CCR6、IL-22）、Treg（TGFB、IL-10）相关分子正性相关。结论 银屑病皮损中RUNX家族表达显著改变,其中RUNX1、3与皮损中的增殖凋亡、T细胞免疫尤其是Th17通路密切相关,可能参与银屑病发病。

Expression of the RUNX family in skin lesions from patients with psoriasis vulgaris

Objective To explore the expression and distribution of runt related transcription factor (RUNX) family in lesions of psoriasis vulgaris (PV), and analyze the correlation between its levels and markers of proliferation, apoptosis and immunity. Methods The transcript levels of RUNX1, 2 and 3 were analyzed in normal skin from 14 healthy controls (HC) and lesions from 17 patients with PV by gene array from a published database. The protein levels and distribution of RUNX1, 2, and 3 were examined by immunohistochemistry (IHC) in normal skin from 11 HC and lesions from 11 patients with chronic eczema (CE) and 12 patients with PV. The correlation between RUNX and other genes in the gene array was analyzed by R, and GO enrichment analysis was performed. Results Compared with HC, the transcript levels of RUNX1 were down regulated (HC: 0.61±0.06, PV: 0.54±0.02, P<0.01), and the levels of RUNX3 were up-regulated in PV lesions (HC: 0.77±0.04, PV: 0.84±0.05, P<0.01), while the expression of RUNX2 showed no differences between the two groups (HC: 0.78±0.05, PV: 0.82±0.04, P=0.18). IHC revealed that RUNX1 was expressed in epidermal keratinocytes and dermal infiltrating inflammatory cells in the skin, while RUNX2 and RUNX3 were more abundant in inflammatory cells. RUNX1 protein levels were down regulated in the epidermis of CE and PV compared to those in HC (HC: 0.24±0.06, PV: 0.11±0.02, CE: 0.11±0.02, HC vs PV: P<0.01, HC vs CE: P<0.01). Compared with HC and CE, the expression of RUNX2 was higher in epidermis of the PV (HC: 0.02±0.01, PV: 0.04±0.02, CE: 0.02±0.02, HC vs PV: P=0.018, PV vs CE: P=0.019). No difference was found in epidermal expression of RUNX3 among three groups (HC: 0.005±0.004, PV: 0.011±0.016, CE: 0.015±0.020, P=0.861). Correlation and functional analysis suggested that the expression of RUNX1 were related to proliferation and apoptosis markers (BCL2A1, WNT2, WNT7B, WNT8A, WNT9B) and Th17 pathway (IL-17A, IL-17F, IL-17E). The genes positively correlated with RUNX3 were mainly participated in the activation and differentiation of T cells and lymphocytes. The genes negatively correlated with RUNX3 involved in negatively regulating the WNT pathway. RUNX3 was positively correlated with Th1 (STAT4, CXCR3, TNF), Th17 (CCR6, IL-22), Treg (TGFB, IL-10) related markers. Conclusion The expression and distribution pattern of RUNX family is significantly altered in skin lesions from PV patients. RUNX1 and RUNX3 are closely related to the signal pathways of proliferation and apoptosis, T cell immunity (especially Th17 pathways) in psoriatic lesions, and may be involved in the pathogenesis of psoriasis.