Renal pericytes express phagocyte/macrophage-like function after kidney injury

肾损伤后肾周细胞表达吞噬细胞/巨噬细胞样功能

• 批准号: 15K19456
• 负责人: W Kittikulsuth
• 金额: $ 2.5万
• 依托单位: Kagawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2015
• 资助国家: 日本
• 起止时间: 2015-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15K19456/
• 关键词: acute kidney injury; pericyte

We have identified that there is an increase in NG2-positive cells, a marker of activated pericyte, expressed in ischemic kidney using 2-kidney 1-clip (2K1I) model as compared to control kidney. Moreover, we discovered that a part of NG2-positive cells is also expressed CD11b or F4/80, a marker of macrophage, in ischemic kidney using flow cytometry and immunohistochemistry. Furthermore, we discovered that expression of NG2/CD11b-positive or NG2/F4/80-positive cells reached the highest level on day3 after ischemia. Next, we isolated NG2-positive cells from ischemic kidney and performed phagocytic ability against fluorescent-conjugated beads. We found that some of NG2-positive cells also contained phagocytic ability against the beads. It is established that phenotype of macrophage can determine severity of renal injury after ischemia. Macrophage can be divided into M1, known as inflammatory macrophage, and M2, known as anti inflammatory macrophage. Therefore, we further checked whether NG2-positive cells are expressed the markers of M1 or M2 macrophage using real-time PCR. We found that NG2-positive cells isolated from ischemic kidney expressed similar level of TNF alpha and IL-6, which is known as M1 markers, as compared to the control kidney. In contrast, NG2-positive cells isolated from ischemic kidney contained a higher level of mannose receptor and IL-10, which is known as M2 markers, as compared to the controls, These results suggest that NG2-positive cells in ischemic kidney contain phenotype of M2 macrophage.

我们已经确定，与对照肾相比，使用2肾1夹（2K 1 I）模型在缺血肾中表达的NG 2阳性细胞（活化周细胞的标志物）增加。此外，我们还通过流式细胞术和免疫组化发现，在缺血肾组织中，部分NG 2阳性细胞也表达CD 11b或巨噬细胞标志物F4/80。 此外，我们发现NG 2/CD 11b阳性或NG 2/F4/80阳性细胞的表达在缺血后第3天达到最高水平。接下来，我们从缺血肾中分离NG 2阳性细胞，并对荧光缀合珠进行吞噬能力。我们发现，一些NG 2阳性细胞也具有对珠粒的吞噬能力。巨噬细胞的表型可以决定缺血后肾损伤的严重程度。 巨噬细胞可分为M1，称为炎症巨噬细胞，和M2，称为抗炎巨噬细胞。因此，我们使用实时PCR进一步检查NG 2阳性细胞是否表达M1或M2巨噬细胞的标志物。我们发现，与对照肾相比，从缺血肾分离的NG 2阳性细胞表达类似水平的TNF α和IL-6，其被称为M1标志物。相反，与对照相比，从缺血肾分离的NG 2阳性细胞含有更高水平的甘露糖受体和IL-10，其被称为M2标记物。这些结果表明，缺血肾中的NG 2阳性细胞含有M2巨噬细胞的表型。