title: The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis.
abstract: Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, and they proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. As chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly, the kidney of CXCR6 knockout mice accumulated fewer bone marrow-derived fibroblasts in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type (WT) mice. CXCR6 deficiency inhibited total collagen deposition and suppressed the expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, WT mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with WT mice engrafted with CXCR6(+/+) bone marrow cells. Transplant of WT bone marrow into CXCR6(-/-) recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may have important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis.
authors.affiliation: 1] Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA [2] Division of Nephrology, Department of Medicine, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jingyin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiaogao
authors.initials: X
authors.lastname: Jin
authors.affiliation: Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, Texas, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Entman
authors.affiliation: 1] Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA [2] Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D018932:Chemokine CCL2 / Q000235:genetics; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D054387:Receptors, CXCR / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000075744:Receptors, CXCR6; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6