Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related InflammationReport as inadecuate




Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related Inflammation - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Juan Yang, Fengming Zhu, Xiaohui Wang, Weiqi Yao, Meng Wang, Guangchang Pei, Zhizhi Hu, Yujiao Guo, Zhi Zhao, Pengge Wang, Jingyi

Source: http://plos.srce.hr/



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