人类系膜增生性肾炎（MsPGN）发病率高，其肾小球系膜细胞（GMC）增生病变是医学界难题之一。亚溶解型（sublytic）C5b-9作为疾病启动原可介导GMC增生。我们的研究发现，大鼠Thy-1肾炎（MsPGN模型）肾组织内和体外用sublytic C5b-9刺激GMC均可激活泛素酶TRAF6、FBXO28（为课题前期筛查到的一种可与TRAF6结合的分子）、信号分子Erk8和转录因子Sp1/c-Myc，并伴有Erk8的泛素化，但FBXO28/TRAF6复合物在大鼠Thy-1肾炎中调控sublytic C5b-9诱导GMC增生的作用并未阐明。因此，本研究拟探讨FBXO28/TRAF6复合物泛素化修饰Erk8调控Sp1/c-Myc活化在sublytic C5b-9引发的Thy-1肾炎GMC增生病变中的作用及机制。旨在揭示大鼠Thy-1肾炎GMC增生的关键靶标，进而为防治人类MsPGN提供依据。

Human mesangial proliferative glomerulonephritis (MsPGN) is a disease with high incidence, which is histologically characterized by marked proliferation of glomerular mesangial cells (GMC). However, the mechanism of GMC proliferation in MsPGN remains unclear. It has been demonstrated that sublytic C5b-9 complex can trigger GMC proliferation. Our previous studies have revealed that the activation of ubiquitin ligase TRAF6, FBXO28（FBXO28 was found to form a complex with TRAF6), signaling molecule Erk8 and transcription factor Sp1/c-Myc as well as the ubiquitination of Erk8 were induced both in the renal tissues of Thy-1 nephritis rats (Thy-1N, a model of MsPGN) and in the GMC exposed to sublytic C5b-9. However the role of FBXO28/TRAF6 complex in the GMC proliferation of rats with Thy-1 nephritis has not been elucidated. Therefore, we attempt to explore the effects of FBXO28/TRAF6 complex-mediated Erk8 ubiquitination and the subsequent Sp1/c-Myc activation on the GMC proliferation induced by sublytic C5b-9 in Thy-1 nephritis and its mechanism. The purpose of this study is to reveal the key mechanism of GMC proliferation in rat Thy-1 nephritis, and further to provide new insights into preventing and treating human MsPGN.