title: Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related Inflammation.
abstract: 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.
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Fifth Hospital of Wuhan, 122 Xianzheng Street, Hanyang district, Wuhan 430050, Hubei, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Wuhan Hamilton Biotechnology-Co.LTD., B6-4, Wuhan institute of biotechnology, #666 Gaoxin Road, Wuhan 430073, Hubei, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Yao
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Guangchang
authors.initials: G
authors.lastname: Pei
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Pengge
authors.initials: P
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Mou
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Liao
authors.affiliation: Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000818:Animals; D001596:Benzylamines; D001853:Bone Marrow / Q000473:pathology*; D017252:CD3 Complex / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D024141:Collagen Type IV / Q000378:metabolism; D000080027:Cyclams; D016207:Cytokines / Q000378:metabolism; D005355:Fibrosis; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D000860:Hypoxia / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D001596:Benzylamines; D017252:CD3 Complex; D024141:Collagen Type IV; D000080027:Cyclams; D016207:Cytokines; D006571:Heterocyclic Compounds; D020797:Receptor, Platelet-Derived Growth Factor beta; C088327:plerixafor