胰岛素样生长因子1上调皮脂腺细胞转录因子Sox9的调控机制及其在痤疮发病中作用

项目名称： 胰岛素样生长因子1上调皮脂腺细胞转录因子Sox9的调控机制及其在痤疮发病中作用

项目编号： No.81201239

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 施歌

作者单位： 广东医学院

项目金额： 23万元

中文摘要： 胰岛素样生长因子1（IGF-1）通过激活PI3K/Akt信号通路引起皮脂大量分泌，在痤疮发病中起关键作用。软骨细胞中IGF-1诱导Sox9表达，Sox9与PI3K/Akt通路互为因果关系。我们已发现IGF-1上调皮脂腺细胞Sox9表达，痤疮皮损中Sox9表达升高，提示IGF-1上调Sox9表达与皮脂分泌和痤疮发病存在联系，但确切调控机制和信号通路不明。我们提出了"IGF-1可能通过PI3K/Akt通路诱导Sox9表达或通过Sox9调控PI3K/Akt通路，进而调节下游转录因子来促进皮脂分泌"的假说。本项目拟主要用Sox9过表达或沉默的腺病毒转染系统、PI3K抑制剂处理SZ95和原代人皮脂腺细胞，观察Sox9对PI3K/Akt通路分子及皮脂分泌的影响。研究结果将揭示IGF-1调控Sox9表达及皮脂分泌的调控机制，确定Sox9与PI3K/Akt通路的关系，为阐明痤疮发病机制提供新思路。

中文关键词： Sox9；胰岛素样生长因子-1；皮脂腺细胞；痤疮；转录因子

英文摘要： Insulin-like growth factor-1 (IGF-1) can stimulate the overproduction of sebum via activation the PI3K/Akt pathway, which is pivotal in the pathogenesis of acne. IGF-1 induces Sox9 expression, and both Sox9 and PI3K/Akt signaling are mutually interacted in chondrocytes. In our previous study, we found that IGF-1 increased Sox9 expression in sebocytes, and overexpression of Sox9 occurred in acne lesions. These results suggest that IGF-1 induced Sox9 upregulation may be related to the sebum secretion and acne development. However, its modulation mechanism and signaling pathway are unknown. Based on the available information, we propose a hypothesis that IGF-1 may induce Sox9 expression via activation of PI3K/Akt pathway or modulate PI3K/Akt pathway via induction of Sox9, followed by regulation of downstream transcription factors to facilitate lipogenesis in sebocytes. To verify our hypothesis, SZ95 cells and primary cultured human sebocytes will be treated with adenovirus expression systems-induced overexpression or knockdown of Sox9 and a PI3K inhibitor, and then the effects of Sox9 on PI3K/Akt signaling molecules and sebum production will be observed. The results will disclose the modulation mechanism of IGF-1 on Sox9 expression and sebum secretion, confirm the relationship between Sox9 and PI3K/Akt pathway, and

英文关键词： Sox9；IGF-1；sebocytes；Acne；transcription factor