VSIG4调控浸润巨噬细胞极化缓解间质性肾炎损伤的机制研究

The protection of renal inflammation injury by macrophage polarization has become the focus of research. Our preliminary findings showed that in UUO model, compared with VSIG4 knockout mice, the tubules and interstitial injury were significantly alleviated in VSIG4 gene expressed mice, and we also found that M2 macrophages associated factors expression was significantly increased. At the same time, the expression of Notch1 was reduced. We suspect that VSIG4 exclusively expressed on macrophages was involved in the regulation of macrophage polarization to alleviate the renal tissue damage. In this study, firstly we will explore the macrophage polarization state of the two groups of mice and the macrophage polarization signaling pathways in vitro. Secondly, we will explore renal interstitial injury in the two groups of UUO model after macrophages transfusion experiments to prove VSIG4 expression is involved in the regulation of interstitial infiltrated macrophages polarization. Our research will investigate if VSIG4 is involved in the regulation of macrophage polarization and the mechanisms for the first time, and the revealing may become a new strategy to regulate macrophage polarization.

巨噬细胞极化在肾脏炎症损伤中的保护作用逐渐成为关注的焦点。前期研究发现：单侧输尿管梗阻模型（UUO）中，VSIG4基因表达小鼠的小管间质损伤与VSIG4基因敲除小鼠相比明显减轻，并且同时发现与M2型巨噬细胞相关因子表达明显升高，Notch1表达下调。结合以往文献我们推测：特异表达于巨噬细胞表面的VSIG4可能通过Notch1参与调控巨噬细胞极化状态的调控，从而发挥巨噬细胞保护功能，减轻肾组织损伤。本课题拟首先分离野生型小鼠和VSIG4敲除小鼠的腹腔巨噬细胞，通过体外培养明确VSIG4的表达与巨噬细胞极化的关系，并进一步探讨Notch1通路在其中发挥的作用；体内通过细胞回输实验进一步验证VSIG4对小鼠巨噬细胞极化和肾组织损伤的影响。本课题研究将首次探讨VSIG4参与调控巨噬细胞极化及其具体分子机制，提示VSIG4有可能成为设计基于巨噬细胞极化调控的新的分子。