人类系膜增生性肾小球肾炎（MsPGN）发病率高，其肾小球系膜细胞（GMC）异常增生引发肾脏纤维化是医学界难题之一。我们发现，大鼠Thy-1肾炎（MsPGN模型）发病早期，肾组织中有GMC增殖反应和促增殖因子（FGF1、PDGFα和TGFβ1）的合成。鉴于转录因子SOX9和有乙酰转移酶活性的转录辅激活因子GCN5及蛋白激酶ERK1/2均是Thy-1肾炎大鼠肾组织和亚溶解型补体攻膜复合物（sublytic C5b-9）诱导GMC同期上调表达的基因，故为了研究sublytic C5b-9启动GMC增生关键分子的作用和翻译后修饰（PTMs）调控机制，本课题拟从体内外探讨SOX9的促增生效应和其同时被GCN5乙酰化及被ERK1/2磷酸化修饰后的交互作用及其对细胞增生和促增殖因子生成的影响，旨在为揭示Thy-1肾炎增生病变的关键分子和PTMs调控机制，并为研发靶向药物和防治人类MsPGN提供科学依据。

Human mesangial proliferative glomerulonephritis (MsPGN) is a disease with high incidence, and the abnormal proliferation of glomerular mesangial cells (GMC) leading to kidney fibrosis is a difficult problem in the medical research field all over the world. Our previous studies have found the proliferative reaction of GMC and the production of some proliferative cytokines (FGF1, PDGFα and TGFβ1) at the early stage of renal tissue in the rats with Thy-1 nephritis ( a model of MsPGN). Given that the transcriptional factor SOX9 and transcriptional coactivator GCN5 with acetyltransferase activity as well as protein kinase ERK1/2 were markedly co-upregulated both in the renal tissue of rat Thy-1 nephritis and in the GMC stimulated with sublytic C5b-9, and in order to elucidate the role and mechanism of some key molecules including post-translation modifications (PTMs) on GMC proliferation triggered by sublytic C5b-9, we attempt to explore the role of SOX9, and the cross-talk effect of acetylated SOX9 by GCN5 and phosphorylated SOX9 by ERK1/2 on the proliferation of GMC and the production of three proliferative cytokines(FGF1, PDGFα and TGFβ1). The purpose of the study is to reveal key molecules role and PTMs mechanism in the renal proliferative lesions of rats Thy-1 nephritis, and further to provide an important evidence for developing drugs and preventing or treating human MsPGN.