EDA1/EDAR通过forkhead转录因子FoxA1调节3D重构汗腺泌汗功能的研究

EDA1/EDAR是调控皮肤附属器发育的关键通路，Foxa1敲除鼠和EDA1突变鼠均表现为无汗。我们前期研究显示：鼠汗腺发育中，EDA1/EDAR在胚芽期和分泌部形成时出现两次高峰；FoxA1在分泌部形成时迅速升高，直到成体。3D重构汗腺中，FoxA1在分泌部分化时开始表达，且FoxA1阳性细胞共表达泌汗相关功能蛋白NKCC1和Na，K-ATPase。因此我们提出“FoxA1是3D重构汗腺泌汗功能的关键作用点，FoxA1通过NKCC1和Na，K-ATPase等调节泌汗；EDA1/EDAR可能参与了FoxA1的激活” 的假说。本项目是在我们已经证实3D重构汗腺与在体汗腺具有相似结构和活体小动物磁共振可用于检测汗腺泌汗功能的基础上，采用磁共振、RNAi、qPCR、WB、三维培养、免疫组化等研究3D重构汗腺的泌汗功能及机制，其结果将为汗腺的修复和再生奠定研究基础，也为临床烧伤的治疗提供科学依据。

EDA1/EDAR is one of the key signal pathways in the development of skin and its appendages. FoxA1 knockout mice and EDA1-mutant mice both reveals complete anhidrosis. Our previous studies showed that in the development of rat eccrine sweat glands, the expression of EDA1/EDAR appeared two peaks, namely sweat gland germ formation and secretory coil formation. FoxA1 was sharply up-regulated from secretory coil formation until adulthood. In 3D reconstituted eccrine sweat glands, the expression of FoxA1 was appeared at the time point that secretory coils began to differentiate, and FoxA1-positive cells co-expressed sweat secretion related functional protein, Na, K-2Cl co-transporter and Na, K-ATPase. Based on the above results, we propose the hypothesis that in the 3D reconstituted eccrine sweat glands, FoxA1 is the central for sweat secretion, which regulates sweat secretion through NKCC1 and Na，K-ATPase, and EDA1/EDAR may be involved in the activation of FoxA1. The study is based on the fact that we have confirmed that the 3D reconstituted eccrine swat glands had similar structures with the native ones and that small animal magnetic resonance imaging could be used to detect sweat secretion, and is involve methods such as magnetic resonance imaging, RNAi, qPCR, WB, three-dimensional cell culture and immunohistochemistry in order to study the sweat secretion function and the related mechanisms of 3D reconstituted eccrine sweat glands. It will lay a foundation for the repair and regeneration of eccrine sweat glands and also provides scientific basis for clinical treatment of burns.