Skin Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeounggi-do, Republic of Korea.
Exp Dermatol. 2010 Apr;19(4):355-62. doi: 10.1111/j.1600-0625.2009.00902.x. Epub 2009 Jul 8.
In the meta-analysis of public microarray databases for different skin diseases, we revealed seven commonly up-regulated genes, DSG3, KRT6, MAP17, PLSCR1, RPM2, SOD2 and SPRR2B. We postulated that the genes selected from the meta-analysis may be potentially associated with the abnormal keratinocyte differentiation. To demonstrate this postulation, we alternatively evaluated whether the genes of interest in the meta-analysis can be regulated by T-helper (Th) cell cytokines in normal human epidermal keratinocytes (NHEK). We found that MAP17 was significantly up-regulated in response to interferon-gamma, interleukin 4 (IL-4), IL-6, IL-17A or IL-22 in NHEK. Interestingly, MAP17 was originally reported to interact with PDZK1; in turn, the PDZK1 gene is localized within the atopic dermatitis-linked region on human chromosome 1q21. In an attempt to evaluate whether MAP17 regulates the expression of cornified envelope-associated genes at the 1q21 locus, such as filaggrin, loricrin and involucrin, we found that the over-expression of MAP17 in HaCaT keratinocytes significantly decreased the expression of filaggrin. Taken together, the Th cell cytokine-induced up-regulation of MAP17 expression may be linked to the down-regulation of filaggrin in NHEK, which may be associated with the abnormal epidermal differentiation observed in the dermatological diseases.
在针对不同皮肤病的公共微阵列数据库的荟萃分析中，我们揭示了七个常见上调的基因，即 DSG3、KRT6、MAP17、PLSCR1、RPM2、SOD2 和 SPRR2B。我们推测，从荟萃分析中选择的基因可能与角质细胞分化异常有关。为了证明这一假设，我们评估了这些在微阵列分析中具有重要意义的基因是否可以在正常人表皮角质细胞（NHEK）中被辅助性 T 细胞（Th）细胞细胞因子调控。我们发现，MAP17 在 NHEK 中受到干扰素-γ、白细胞介素 4（IL-4）、IL-6、IL-17A 或 IL-22 的刺激后显著上调。有趣的是，MAP17 最初被报道与 PDZK1 相互作用；反过来，PDZK1 基因定位于人类染色体 1q21 的特应性皮炎相关区域。我们试图评估 MAP17 是否调节 1q21 位点上的颗粒层相关基因（如丝聚蛋白、兜甲蛋白和内披蛋白）的表达，发现 HaCaT 角质细胞中 MAP17 的过表达显著降低了丝聚蛋白的表达。总之，Th 细胞细胞因子诱导的 MAP17 表达上调可能与 NHEK 中丝聚蛋白的下调有关，这可能与皮肤病中观察到的表皮分化异常有关。
