睾酮通过上调EGFR信号通路调控视网膜铁调素的实验研究

Age related macular degeneration(AMD) may be related with iron mediated oxidative stress. As an important regulator of iron metabolism, hepcidin expression is suppressed by EGF according to related studies. Our previous studies have confirmed that testosterone abides to activating expression of EGFR. Accordingly, we hypothesis that testosterone suppressed hepcidin expression by activating EGFR. To verify this above-mentioned mechanism and clarify the claim that testosterone may modulate hepcidin by activated EGFR signal pathways, this program is scheduled to explore changes of hepcidin expression and EGFR via technologies like immunofluorescence staining, Perls’ stainning, real time PCR and Western Blot by virtue of testosterone changes and exogenous EGFR-specific inhibitor at ARPE19 cell lines and iron-overloaded mice models（Bmp6 knock out）. This program is believed to detail mechanism of retinal iron metabolism and highlight prospect for AMD prevention and treatment once completed.

年龄相关性黄斑变性（AMD)可能与铁介导的氧化应激损伤有关。铁调素是机体对铁调控的重要因子。研究表明表皮生长因子（EGF）可以抑制铁调素的表达，我们的前期实验研究发现睾酮可以激活表皮生长因子受体(EGFR)的表达，因此我们提出假说：睾酮可能通过上调EGFR而抑制铁调素的表达。为明确这一调控机制，本项目拟在ARPE19细胞与铁过载小鼠模型（Bmp6 敲除）上，分别通过改变睾酮水平及加入EGFR特异性阻断剂进行干预，使用免疫荧光、real time PCR、Perls’染色、Western Blot等技术观察铁调素与EGFR的变化，以明确睾酮可能依赖于激活EGFR信号通路对铁调素产生调控。本课题的完成，将使视网膜铁代谢调控机制进一步明确，并可能为AMD的防治提供新的思路。