管周毛细血管功能障碍是急性肾损伤走向慢性化的重要环节。管周毛细血管内皮细胞表达C型凝集素能够招募循环单核细胞，参与组织损伤，但是具体机制不清楚。申请人前期工作发现，在急性肾损伤后修复的小鼠肾组织中，C型凝集素家族成员Collectin-12蛋白编码基因转录及翻译水平显著升高。同时Collectin-12潜在受体DC-SIGN及下游信号分子CFP基因表达也显著上调，而C型凝集素的竞争性受体CD72表达下降。故推测Collectin-12可能作为血管内皮细胞释放的信号分子，通过结合单核细胞表面DC-SIGN受体，激活单核细胞及补体旁路途径，加重肾小管损伤。本项目拟通过建立血管内皮细胞条件性Colec12基因敲除小鼠，及自主开发的Collectin-12胞外结构域竞争性模拟剂，验证内皮细胞Collectin-12在肾小管损伤中的作用，并测试Collectin-12模拟剂在肾小管损伤中的治疗作用。

The impairment of the peritubular capillary (PTC) is important in the chronicization of AKI. The PTCs are involved in tissue damage and repair via transportation and activation of immune cells including monocytes, but the underlying mechanism is unclear. It is known that the C-type lectin expressed by vascular endothelial cells recruits and activates peripheral monocytes. Prior work by the applicant found that the Colec12 gene expression significantly increases at both transcription level and translational level in the kidney tissue after acute renal injury. At the same time, the gene expression of the collectin-12 potential receptor DC-SIGN and the downstream signaling molecule CFP was significantly increased, and the expression of CD72, the competitive receptor of C-type lectin, decreased. Therefore, it is speculated that Collectin-12 may be an important intermediary for the release of vascular endothelial cells by binding to the DC-SIGN receptor on the surface of the monocytes to activate the complement bypass pathway within the monocytes, thereby aggravating the damage to the renal tubule. This project aims to verify the function of the Colec12 gene in acute kidney injury and repair, by establishing a microvascular endothelial-specific Colec12 gene knockout mice, as well as a competitive analog agent of the extracellular segment of collectin-12 protein, which is supposedly binds with the DC-SIGN receptor on the monocyte surface in competition with collectin-12, thus damping the alternative pathway complement cascade and protecting renal tubular injury.