炎症反应在肾缺血再灌注损伤的发生发展中起关键作用，但其发生和精确调控仍不完全清楚。我们前期研究发现：缺血再灌注损伤后肾脏组织中类泛素蛋白FAT10的表达上调，敲除FAT10明显减轻肾脏组织损伤以及改善肾功能；在肾小管上皮细胞中，沉默FAT10可抑制NF-κB信号通路的活化，而且减少趋化因子RANTES的产生。据此我们假设：在肾缺血再灌注损伤中，FAT10通过激活NF-κB信号通路促进趋化因子RANTES的产生，进而加重炎症反应，导致肾脏组织损伤。本申请通过体内注射RNATES中和抗体、流式细胞术结合病理学等技术探讨FAT10调控肾缺血再灌注损伤的作用和分子机制；采用慢病毒载体、流式微球分析技术及Co-IP等手段研究FAT10通过NF-κB信号通路调控RANTES产生的分子机制。本研究将阐明FAT10通过调控炎症反应促进肾缺血再灌注损伤的分子机制，为寻找和筛选新的药物靶点提供重要的科学依据。

Inflammation play an important role in the development of renal ischemia-reperfusion injury (RIRI), but its regulation mechanism is unclear. Our preliminary studies suggest that the ubiquitin-like protein FAT10 expression was elevated in tubular epithelial cell after RIRI；Knockout of FAT10 alleviated morphologic damage after RIRI, protecting from deterioration of kidney function. Furthermore, In vitro experiments indicate that FAT10 silence abrogated NF-κB signaling activation and reduced the induction of chemokine RANTES in tubular epithelial cells. Consequently, we hypothesize that the upregulation of FAT10 in renal tubular cells may promotes RANTES expression via activation of NF-κB signaling, and then aggravates renal inflammation, leading to tissue damage after RIRI. To determine the critical roles of FAT10 in post-RIRI inflammatory response leading to kidney injury, we will use WT and FAT10 knockout mice undergoing renal artery clamp models of ischemia-reperfusion injury in combining with RANTES neutralizing antibody injection in vivo, flow cytometry and pathological analysis. Moreover, to evaluate the effect of FAT10 on RANTES expression via NF-κB signaling pathway, we will employ the Lentiviral vector, Co-Immunoprecipitation (Co-IP), Cytometric bead array (CBA) and other methods. The proposed studies will provide new knowledge regarding the molecular mechanisms of how FAT10 participates the pathogenesis of renal ischemia-reperfusion injury through promoting inflammation, and provide the theoretical and experimental basis for intervention of acute kidney injury after RIRI.