R.intestinalis通过Sp3磷酸化介导TLR5转录激活在溃疡性结肠炎的抗炎分子机制研究

溃疡性结肠炎发病机制不明，肠道菌群作用重要。本课题组前期研究发现肠罗斯拜瑞菌氏菌（R.intestinalis）在其中发挥了重要抗炎保护作用，R.intestinalis通过其主要代谢产物丁酸，调节转录因子Sp3与R.intestinalis鞭毛蛋白的主要受体Toll样受体5(TLR5)的启动子区结合，激活TLR5的转录表达，发挥抗炎作用。深入研究发现其具体的分子机制可能与Sp3的磷酸化状态结合TLR5启动子区相关，目前国内外未见相关报道。因此本课题拟通过体外和体内研究，使用PKCδ-/-小鼠、MEK抑制剂、ERK抑制剂、ChIP分析技术等，明确R.intestinalis通过代谢产物丁酸，介导PKCδ/MEK/ERK1/2信号通路磷酸化Sp3，增强p300募集和组蛋白乙酰化，激活TLR5转录的新机制，明确R.intestinalis在溃疡性结肠炎抗炎作用的分子机制。

The pathogenesis of ulcerative colitis is unknown, and the role of intestinal flora is important. The previous research of this research group found that R. intestinalis played an important anti-inflammatory protection role. R. intestinalis regulated the transcription factors Sp3 and R. intestinalis flagellin through its main metabolite butyric acid. The promoter region of the only receptor Toll-like receptor 5 (TLR5) binds, activates the transcriptional expression of TLR5, and exerts an anti-inflammatory effect. In-depth study found that the specific molecular mechanism may be related to the phosphorylation state of Sp3 combined with the TLR5 promoter region, and no relevant reports have been reported at home and abroad. Therefore, this subject intends to use PKCδ-/-mice, MEK inhibitors, ERK inhibitors, ChIP analysis technology, etc. through in vitro and in vivo studies to clarify the metabolite butyric acid of R.intestinalis and pass PKCδ / MEK / ERK1 / 2 signal The pathway phosphorylates Sp3, enhances p300 recruitment and histone acetylation, activates a new mechanism of TLR5 transcription, and clarifies the molecular mechanism of R.intestinalis's anti-inflammatory effect in ulcerative colitis.