Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related Inflammation.
Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related Inflammation.
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连续 AMD3100 治疗通过调节骨髓来源的促血管生成细胞归巢和 T 细胞相关炎症来恶化肾纤维化
DOI：
10.1371/journal.pone.0149926
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yao Y
中科院分区：
文献类型：
--
作者：
Yang J;Zhu F;Wang X;Yao W;Wang M;Pei G;Hu Z;Guo Y;Zhao Z;Wang P;Mou J;Sun J;Zeng R;Xu G;Liao W;Yao Y
AMD3100是一种趋化因子受体4型（CXCR4）的小分子抑制剂，位于CD34+细胞和多种炎症细胞的细胞膜中，有报道称其可减少肺、肝和心肌的器官纤维化。然而，AMD3100对肾纤维化的作用尚不清楚。本研究探讨了AMD3100对肾纤维化的影响。C57bl/6小鼠分别给予或不给予AMD3100单侧输尿管梗阻（UUO）手术。采用组织染色、免疫细胞化学和Western Blot检测和分析小管损伤、胶原沉积和纤维化情况。采用流式细胞术（FACS）和免疫荧光（IF）检测骨髓源性血管生成前细胞（CD45+、CD34+和CD309+细胞）和毛细血管密度（CD31+）。炎症细胞、趋化因子和T细胞增殖的特征。我们发现AMD3100治疗并没有减轻肾纤维化，反而增加了组织损伤和肾纤维化。持续给药AMD3100并没有改善骨髓源性促血管生成细胞的动员，反而抑制了骨髓源性促血管生成细胞向纤维化肾脏的迁移。此外，与未处理肾脏相比，amd3100处理肾脏的T细胞浸润显著增加。因此，用AMD3100治疗UUO小鼠导致T细胞浸润增加，表明AMD3100加重了肾纤维化。
AMD3100 is a small molecule inhibitor of chemokine receptor type 4 (CXCR4), which is located in the cell membranes of CD34+ cells and a variety of inflammatory cells and has been reported to reduce organ fibrosis in the lung, liver and myocardium. However, the effect of AMD3100 on renal fibrosis is unknown. This study investigated the impact of AMD3100 on renal fibrosis. C57bl/6 mice were subjected to unilateral ureteral obstruction (UUO) surgery with or without AMD3100 administration. Tubular injury, collagen deposition and fibrosis were detected and analyzed by histological staining, immunocytochemistry and Western Blot. Bone marrow derived pro-angiogenic cells (CD45+, CD34+ and CD309+ cells) and capillary density (CD31+) were measured by flow cytometry (FACS) and immunofluorescence (IF). Inflammatory cells, chemotactic factors and T cell proliferation were characterized. We found that AMD3100 treatment did not alleviate renal fibrosis but, rather, increased tissue damage and renal fibrosis. Continuous AMD3100 administration did not improve bone marrow derived pro-angiogenic cells mobilization but, rather, inhibited the migration of bone marrow derived pro-angiogenic cells into the fibrotic kidney. Additionally, T cell infiltration was significantly increased in AMD3100-treated kidneys compared to un-treated kidneys. Thus, treatment of UUO mice with AMD3100 led to an increase in T cell infiltration, suggesting that AMD3100 aggravated renal fibrosis.