Role of EP4 receptor-associated protein in regulating macrophage activation

在本研究中，我们旨在剖析EP4受体相关蛋白EPRAP的意义和病理生理作用，EPRAP是一种新的巨噬细胞激活的细胞质调节因子。我们产生了EPRAP基因缺陷的小鼠，以及EPRAP在巨噬细胞中特异表达的转基因小鼠。我们用这些小鼠建立了人类炎症性肠病和肺纤维化的动物模型。在这两个实验中，EPRAP缺乏显著增加了浸润性巨噬细胞的激活和局部炎症，导致存活率显著下降。此外，我们还发现EPRPA减轻了炎症病变中MEK-ERK通路的激活，并抑制了巨噬细胞的激活。我们的结果表明，EPRAP通过调节体内巨噬细胞的激活，在各种炎症性疾病的发生和转归中发挥重要作用。

In this study we aimed to dissect the significance and pathophysiological roles of EP4 receptor-associated protein, EPRAP, a novel cytoplasmic regulator of macrophage activation. We generated EPRAP-deficient mice as well as transgenic mice with enforced expression of EPRAP specifically in macrophages. We used these mice and created animal models of human inflammatory bowel diseases and pulmonary fibrosis. In both experiments, EPRAP deficiency markedly increased infiltrated macrophage activation and local inflammation, resulting in significant decrease in survival rates. In addition, we figured out that EPRPA mitigated the MEK-ERK pathway activation and inhibited macrophage activation in the inflamed lesions. Our results indicated that EPRAP plays crucial roles in the pathogenesis and outcome of various inflammatory diseases by regulating macrophage activation in vivo.