肾脏缺血再灌注损伤是影响移植肾短期及长期存活的重要因素，其机制尚不清楚。miR-17-92基因簇是一个高度保守的基因簇，编码多个miRNA。我们前期研究发现肾脏缺血再灌注损伤后miR-17-92家族有多个miRNA水平明显增高，且miR-17-92高表达具有肾脏保护作用。研究表明TSP-1/CD47信号轴激活会加重肾脏缺血再灌注损伤，抑制TSP-1/CD信号轴能够明显激活细胞再生及损伤后修复信号；生物信息学分析发现miR-17-92簇有多个miRNA能够直接靶向TSP-1。因此我们提出在肾缺血再灌注损伤中，miR-17-92可以通过靶向TSP-1，抑制TSP-1/CD47信号轴，抑制其下游损伤信号通路、上调再生信号通路，从而保护肾脏。本项目拟通过多种分子生物学手段，明确miR-17-92在肾脏缺血再灌注损伤中发挥作用的具体miRNAs，并阐明其对于TSP/CD47信号轴的调控机制。

Renal ischemia reperfusion injury (IRI) is associated with reduced short-term and long-term outcome of kidney transplantation. The mechanism is not well addressed and no cure is available. miR-17-92 cluster which encodes miR-17, miR-18a, miR-19a, miR-20a, miR-19b is highly conservative. We found several miRNAs of miR-17-92 cluster increased after IRI and miR-17-92 served as a protector in renal.IRI. Few studies have suggested that the activation of TSP-1/CD47 axis worsen renal IRI, and inhibition of TSP-1/CD47 axis promoted the upregulation of vascular regeneration signal and cellular self-renewal signal after injury.Bio-information analysis revealed that miR-17-92 can target the 3’UTR of TSP-1. Therefore, we hypothesized miR-17-92 may targeting TSP-1, result in the inhibition of TSP-1/CD47 axis, then down regulating the injury signal and upregulating regeneration signal in renal IRI, leading to a better kidney function preservation. In the present research, we plan to utilize comprehensive molecular methods to test our hypothesis, and find the key member of miR-17-92 cluster which played important role in kidney protection.