title: CXCR6 plays a critical role in angiotensin II-induced renal injury and fibrosis.
abstract: OBJECTIVE
  Recent studies have shown that angiotensin II (Ang II) plays a critical role in the pathogenesis and progression of hypertensive kidney disease. However, the signaling mechanisms are poorly understood. In this study, we investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis.
  
  
  RESULTS
  Wild-type and CXCR6-green fluorescent protein (GFP) knockin mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg per minute after unilateral nephrectomy for ≤ 4 weeks. Wild-type and CXCR6-GFP knockin mice had virtually identical blood pressure at baseline. Ang II treatment led to an increase in blood pressure that was similar between wild-type and CXCR6-GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts and produced less extracellular matrix protein in the kidneys after Ang II treatment. Furthermore, CXCR6-GFP knockin mice exhibited fewer F4/80(+) macrophages and CD3(+) T cells and expressed less proinflammatory cytokines in the kidneys after Ang II treatment. Finally, wild-type mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the kidney after Ang II treatment when compared with wild-type mice engrafted with CXCR6(+/+) bone marrow cells.
  
  
  CONCLUSIONS
  Our results indicate that CXCR6 plays a pivotal role in the development of Ang II-induced renal injury and fibrosis through regulation of macrophage and T-cell infiltration and bone marrow-derived fibroblast accumulation.
authors.affiliation: From the Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX (Y.X., X.J., J.Y., Y.W.); Division of Nephrology, Department of Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Y.X.); Division of Cardiovascular Sciences, Department of Medicine and the DeBakey Heart Center, Baylor College of Medicine and The Methodist Hospital, Houston, TX (M.L.E.); and Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (Y.W.).
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: From the Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX (Y.X., X.J., J.Y., Y.W.); Division of Nephrology, Department of Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Y.X.); Division of Cardiovascular Sciences, Department of Medicine and the DeBakey Heart Center, Baylor College of Medicine and The Methodist Hospital, Houston, TX (M.L.E.); and Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (Y.W.).
authors.forename: Xiaogao
authors.initials: X
authors.lastname: Jin
authors.affiliation: From the Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX (Y.X., X.J., J.Y., Y.W.); Division of Nephrology, Department of Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Y.X.); Division of Cardiovascular Sciences, Department of Medicine and the DeBakey Heart Center, Baylor College of Medicine and The Methodist Hospital, Houston, TX (M.L.E.); and Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (Y.W.).
authors.forename: Jingyin
authors.initials: J
authors.lastname: Yan
authors.affiliation: From the Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX (Y.X., X.J., J.Y., Y.W.); Division of Nephrology, Department of Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Y.X.); Division of Cardiovascular Sciences, Department of Medicine and the DeBakey Heart Center, Baylor College of Medicine and The Methodist Hospital, Houston, TX (M.L.E.); and Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (Y.W.).
authors.forename: Mark L
authors.initials: ML
authors.lastname: Entman
authors.affiliation: From the Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX (Y.X., X.J., J.Y., Y.W.); Division of Nephrology, Department of Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Y.X.); Division of Cardiovascular Sciences, Department of Medicine and the DeBakey Heart Center, Baylor College of Medicine and The Methodist Hospital, Houston, TX (M.L.E.); and Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (Y.W.). yanlinw@bcm.edu.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D000075744:Receptors, CXCR6; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: C482906:Cxcr6 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D000804:Angiotensin II; D049452:Green Fluorescent Proteins
keywords: CC chemokine receptor; angiotensin II; fibrosis; inflammation