巨噬细胞中溶酶体相关跨膜蛋白5（LAPTM5）在急性肺损伤中的功能及机制研究

急性肺损伤是高病死率的呼吸系统高危重症，临床上尚无有效治疗策略。巨噬细胞招募、活化介导的炎症激活是急性肺损伤的关键发病因素。本项目前期通过公共数据库挖掘筛选和实验验证，明确了溶酶体相关跨膜蛋白5(LAPTM5)在急性肺损伤发生后显著下调，Laptm5敲除小鼠表现出加重脂多糖诱导的肺部通透性增加和炎症反应，且Laptm5主要的效应细胞为骨髓源细胞，同时肺脏单细胞转录组提示其仅在巨噬细胞中特异高表达。因此我们提出科学假设：LAPTM5抑制急性肺损伤中巨噬细胞介导的炎症反应，发挥保护功能。本项目拟借助Laptm5敲除、转基因小鼠和体内外急性肺损伤模型，采用高通量测序、质谱技术联合分子生物学实验，从动物、细胞、分子水平探讨LAPTM5在急性肺损伤中的功能及机制。本项目将为系统理解急性肺损伤调控网络提供新思路，为急性肺损伤及其他呼吸重症的防治提供新靶点，开发新策略。

Acute lung injury (ALI) is a high-risk respiratory disease with high mortality, but there is no effective treatment strategy. Inflammatory activation mediated by macrophages recruitment and activation is the key pathogenesis of acute lung injury. In preliminary study, through public databases mining and experiments, we confirmed that lysosomal-associated protein transmembrane 5 (LAPTM5) was significantly down-regulated after acute lung injury. In addition, Laptm5 knockout mice showed increased pulmonary permeability and inflammation activation induced by lipopolysaccharide, the main effector cells of Laptm5 were bone marrow-derived cells and Laptm5 was only highly expressed in macrophages based on a lung single cell RNA-Seq database. In summary, we hypothesized that LAPTM5 can protect acute lung injury by inhibiting the inflammatory response of macrophages. This project intends to use Laptm5 knockout and transgenic mice, acute lung injury models in vivo and in vitro, with the help of high-throughput sequencing and mass spectrometry technology, molecular biology experiments, to explore the function and molecular mechanism of LAPTM5 in acute lung injury at animal, cellular and molecular levels. This project will systematically understand the regulatory network of acute lung injury, and provide new targets and strategies for the prevention and treatment of acute lung injury or other severe respiratory diseases.