p53是重要的抑癌基因之一，新近发现p53参与调控纤维化，但对肾纤维化的作用及机制仍不完全清楚。因此，本项目拟采用梗阻性肾病（UUO)模型，探讨p53调控肾纤维化的作用及机制。预实验显示通过pif-a抑制p53显著减轻UUO模型肾纤维化，microRNAs芯片表达谱、Real time PCR和Northern blot证明pif－a干预UUO组显著下调miR-215-5p、-199a-5p和-199a-3p的表达。为此，本项目拟通过抑制p53探讨TGF-β上调上述miRs的分子机制，证明上述miRs调控相应的预测靶基因CTNNBIP1、Caveolin1和SOCS7的表达，深入阐明上述靶基因调控纤维化的信号机制，并使用p53敲除小鼠UUO模型和CKD（IgA肾病、糖尿病肾病和高血压肾病）患者肾活检的标本揭示其抗纤维化的作用及机制，为抑制p53抗纤维化提供科学的理论依据和新的防治靶点。

P53 is one of the important cancer gene suppression, we showed p53 regulates multiple gene classes to protect against acute kidney injury, the newly study indicated that p53 involved in the fibrosis regulation, but the role of fibrosis was exactly opposite in different organs and models. Therefore, this project intends to use the classic renal fibrosis model of unilateral ureteral obstruction (UUO), and investigate the role and molecular mechanism of p53 on TIF. Recent studies showed that miRNA also involved in the regulation of renal fibrosis. Pre-experiment demonstrated that inhibition p53 with pif-a significantly ameliorated renal fibrosis in UUO model, and significantly down-regulated expression of miR-215-5p, -199a-5p and -199a-3p using microRNAs chip, which was further confirmed by Real time PCR and Northern blot ways. Therefore, this project will explore the role and molecular mechanism of p53 on expression of miR-215-5p, -199a-5p and -199a-3p. Furthermore, the predicted direct target genes and related signal pathway,CTNNBIP1, Caveolin1 and SOCS7, were respectively regulated by miR-215-5p, -199a-5p and -199a-3p, which need to be demonstrated. To establish UUO mice model with p53 knockout, and kidney samples from CKD (IgA nephropathy, diabetic nephropathy and renal biopsy in patients with hypertensive nephropathy) patients will reveal p53 anti-fibrosis role and above molecular mechanism. This study will elucidate the molecular mechanism of p53 anti-fibrosis and provide scientific theoretical and a new target for the prevention of renal fibrosis from cells, animal, people in three levels.