title: CXCL16 recruits bone marrow-derived fibroblast precursors in renal fibrosis.
abstract: Although fibroblasts are responsible for the production and deposition of extracellular matrix in renal fibrosis, their origin is controversial. Circulating fibroblast precursors may contribute to the pathogenesis of renal fibrosis, but the signaling mechanisms underlying the recruitment of bone marrow-derived fibroblast precursors into the kidney in response to injury are incompletely understood. Here, in the unilateral ureteral obstruction model of renal fibrosis, tubular epithelial cells upregulated the chemokine CXCL16 in obstructed kidneys, and circulating fibroblast precursors expressed the CXCL16 receptor, CXCR6. Compared with wild-type mice, CXCL16-knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors in obstructed kidneys. CXCL16-knockout mice also exhibited significantly fewer CD45-, collagen I-, and CXCR6-triple-positive fibroblast precursors in injured kidneys. Furthermore, targeted deletion of CXCL16 inhibited myofibroblast activation, reduced collagen deposition, and suppressed expression of collagen I and fibronectin. In conclusion, CXCL16 contributes to the pathogenesis of renal fibrosis by recruiting bone marrow-derived fibroblast precursors.
authors.affiliation: Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Song-Chang
authors.initials: SC
authors.lastname: Lin
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Chen
authors.forename: Liqun
authors.initials: L
authors.lastname: He
authors.forename: Feixia
authors.initials: F
authors.lastname: Dong
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Shuhua
authors.initials: S
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Mark L
authors.initials: ML
authors.lastname: Entman
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000166:cytology; D009400:Nephrosclerosis / Q000209:etiology / Q000378:metabolism*; D054387:Receptors, CXCR / Q000378:metabolism; D000075744:Receptors, CXCR6; D014517:Ureteral Obstruction
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6