系膜增生性肾炎是导致慢性肾脏病的主要病因, 而治疗该疾病的关键环节就是有效地抑制系膜细胞增殖。因此，阐明系膜细胞增殖的分子调控机制，将为系膜增殖性肾炎的临床治疗提供新的思路和理论依据。我们的前期研究发现转录因子KLF15可以抑制系膜细胞的增殖，但其具体的分子机制尚不清楚。本课题拟采取先进的ChIP-seq联合SILAC-LC/MS 技术，对KLF15抑制系膜细胞增殖的靶向调控基因及其结合位点，以及相关通路进行系统的生物学深度分析，描绘出KLF15调控系膜细胞增殖的分子网络。构建KLF15的基因修饰小鼠并建立系膜增生性肾炎模型，验证上述靶基因及相应分子网络的变化特点以及与肾脏病理改变、肾功能的变化关系。通过上述研究，我们期望揭示转录因子KLF15在系膜细胞增生性肾炎中调控系膜细胞增殖的分子机制，筛选出针对系膜增殖性肾炎的治疗靶点，为新药的研发和系膜增殖性肾炎的有效治疗打下坚实的理论基础。

Mesangial proliferative glomerulonephritis is a major cause of chronic kidney disease, and to inhibit the proliferation of mesangial cells effectively is the key point to treat it. Therefore, to clarify the molecular mechanism of mesangial cell proliferation, would provide new ideas and theoretical basis to clinical treatment of mesangial proliferative glomerulonephritis. Our previous study found that the transcription factor KLF15 can inhibit the proliferation of mesangial cells. But the exact molecular mechanism is unclear. This project intends to adopt advanced technology ChIP-seq couple with SILAC-LC/MS to analysis deeply the target regulation gene, binding sites as well as the biological pathways of KLF15 inhibiting mesangial cell proliferation, then presentate the molecular networks of KLF15 regulation mesangial cell proliferation. Soon after, basing on building KLF15 gene modified mice and establishing mesangial proliferative glomerulonephritis model, we verify the characteristics of changes about these target genes and molecular networks, identify the relationship between these changes and pathological, renal function. Through these studies, we hope to reveal the molecular mechanisms regulating cell proliferation of the transcription factor KLF15 in mesangial proliferative glomerulonephritis, and screened the therapeutic target for mesangial proliferative glomerulonephritis, it will provide a solid theoretical foundation for developing new drugs and effective treatment about mesangial proliferation glomerulonephritis.