Renal Macrophage Migration and Crystal Phagocytosis via Inflammatory-Related Gene Expression During Kidney Stone Formation and Elimination in Mice: Detection by Association Analysis of Stone-Related Gene Expression and Microstructural Observation
Renal Macrophage Migration and Crystal Phagocytosis via Inflammatory-Related Gene Expression During Kidney Stone Formation and Elimination in Mice: Detection by Association Analysis of Stone-Related Gene Expression and Microstructural Observation
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DOI：
10.1002/jbmr.158
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发表时间：
2010-12-01
影响因子：
6.2
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Okada, Atsushi;Yasui, Takahiro;Kohri, Kenjiro
小鼠具有很强的清除肾脏草酸钙结晶的能力，我们以前的研究表明单核细胞-巨噬细胞相互作用可能参与了这种现象的易感性。为了阐明巨噬细胞相关因子在防止小鼠肾脏草酸钙结晶形成中的作用，进行基于微阵列途径分析的形态学和表达研究。给8周龄雄性C57 BL/6 N小鼠施用80 mg/kg的抗肿瘤药物。kg乙醛酸，每3天提取肾脏用于DNA微阵列分析。基于微阵列分析的原始数据，炎症反应的途径分析证明通过增加趋化因子（C-X-C）配体1，纤连蛋白1，和主要组织相容性（MHC）II类通过定量逆转录聚合酶链反应（RT-PCR）进行的相关基因表达值的关联分析表明趋化因子（C-C）配体2、CD 44、集落刺激因子1、纤连蛋白1基质gla蛋白、分泌型磷蛋白1和转化生长因子β 1（TGF-β 1）与肾晶体和F4/80（一种巨噬细胞标志物）的量的关系免疫组化，在实验过程中间质巨噬细胞增加，CD 44和MHCII类在晶体周围上调，形成部位通过透射电子显微镜对肾巨噬细胞的超微结构观察表明间质巨噬细胞迁移伴随晶体的吞噬作用总之，晶体形成和沉积诱导的肾小管细胞炎症相关基因表达增加可通过CD 44与骨桥蛋白和纤维连接蛋白的相互作用诱导单核-巨噬细胞迁移和吞噬。通过吞噬和消化去除巨噬细胞的能力可能成为预防结石形成的新靶点（C）2010年美国骨与矿物质研究学会
Mice have a strong ability to eliminate renal calcium oxalate crystals, and our previous examination indicated a susceptibility in which monocyte-macrophage interaction could participate in the phenomenon To clarify the macrophage-related factors playing roles in the prevention of crystal formation in mouse kidneys, morphologic and expression studies based on microarray pathway analysis were performed Eight-week-old male C57BL/6N mice were administered 80 mg/kg of glyoxylate by daily intraabdominal injection for 15 days, and the kidneys were extracted every 3 days for DNA microarray analysis Based on the raw data of microarray analysis, pathway analyses of inflammatory response demonstrated macrophage activation through the increased expression of chemokine (C-X-C) ligand 1, fibronectin 1, and major histocompatability (MHC) class II Association analysis of related gene expression values by quantitative reverse transcription polymerase chain reaction (RT-PCR) indicated the high association of chemokine (C-C) ligand 2, CD44, colony-stimulating factor 1, fibronectin 1, matrix gla protein, secreted phosphoprotein 1, and transforming growth factor beta 1 (TGF-beta 1) with the amount of both renal crystals and F4/80, a macrophage marker Immunohistochemically, interstitial macrophages increased during the experimental course, and CD44 and MHC class II were upregulated around crystal-formation sites Ultrastructural observation of renal macrophages by transmission electron microscopy indicated interstitial macrophage migration with the phagocytosis of crystals In conclusion, increased expression of inflammation-related genes of renal tubular cells induced by crystal formation and deposition could induce monocyte-macrophage migration and phagocytosis via the interaction of CD44 with osteopontin and fibronectin Such crystal-removing ability of macrophages through phagocytosis and digestion might become a new target for the prevention of stone formation (C) 2010 American Society for Bone and Mineral Research