急性肾损伤（AKI）是一类临床常见的危重疾病，进展快，死亡率高。肾近曲小管细胞的线粒体凋亡途径与AKI修复密切相关，分子机制尚不清。基于我们自科项目（81572076）支持构建的Ttc36敲除小鼠，建立AKI小鼠模型，发现Ttc36敲除后的肾损伤程度与野生型相比明显加重；且TTC36表达量与AKI修复程度呈负相关。细胞水平，TTC36能抑制肾近曲小管细胞的凋亡，影响线粒体分布和形态。本项目研究TTC36在AKI修复中的作用和分子机制。基于Ttc36基因敲除小鼠，拟分别构建体内、外AKI模型，通过干预TTC36，检测其对肾形态和功能，肾近曲小管细胞凋亡及线粒体功能的影响；深入探寻TTC36是否通过调控线粒体影响肾近曲小管细胞凋亡过程。综上，阐明TTC36在AKI修复中的具体分子机制，提供研发TTC36小分子治疗药物的依据，建立AKI修复评估的新指标，拓展AKI早期干预治疗的新思路。

Acute kidney injury (AKI) is a common clinical critically disease with rapid progression and high mortality. The apoptosis of renal proximal tubule cells and mitochondrial function are both closely related to the progress and repair of AKI. However, the molecular mechanisms remain largely unknown. With the support of our Natural Science Foundation of China (81572076), we successfully established Ttc36 homozygous knockout mice. We further constructed AKI mouse model, and found that Ttc36-/- mice showed increasingly degree of damage compared to the wild type. Moreover，the expression of TTC36 was negatively correlated with the repair level of AKI. At the cellular level, overexpression of TTC36 could inhibit proximal tubule cell apoptosis and disrupt mitochondrial distribution and morphology. Based on the above results, we intend to investigate functions and molecular mechanisms of TTC36 in AKI repair process. In this study, we propose to assess the alteration of renal morphology and function, renal proximal tubule cells apoptosis as well as mitochondrial features by intervening TTC36 in AKI model. Furthermore, we will explore in depth about the mechanism of TTC36 in AKI repair process which is dependent on mitochondrial-mediated apoptosis of renal proximal tubule cells. Ultimately, our work will clarify the molecular mechanism of TTC36 in AKI，and provide a potential marker for AKI repair appraisal. More importantly, the available of preparing TTC36 chemical analogue due to low molecular weight sheds the light on a new solution for AKI therapy.