title: The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature.
abstract: CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1) is a unique homeostatic chemokine that signals through its cognate receptor, CXCR4. CXCL12/CXCR4 signaling is essential for the formation of blood vessels in the gastrointestinal tract during development, but its contribution to renal development remains unclear. Here, we found that CXCL12-secreting stromal cells surround CXCR4-positive epithelial components of early nephrons and blood vessels in the embryonic kidney. In glomeruli, we observed CXCL12-secreting podocytes in close proximity to CXCR4-positive endothelial cells. Both CXCL12- and CXCR4-deficient kidneys exhibited identical phenotypes; there were no apparent abnormalities in early nephrogenesis or in differentiation of podocytes and tubules, but there was defective formation of blood vessels, including ballooning of the developing glomerular tuft and disorganized patterning of the renal vasculature. To clarify the relative importance of different cellular defects resulting from ablation of CXCL12 and CXCR4, we established endothelial cell-specific CXCR4-deficient mice, which recapitulated the renal phenotypes of conventional CXCR4-deficient mice. We conclude that CXCL12 secreted from stromal cells or podocytes acts on endothelial cells to regulate vascular development in the kidney. These findings suggest new potential therapeutic targets for remodeling the injured kidney.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine (B6), Suita, Japan. takaba@kid.med.osaka-u.ac.jp
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Takabatake
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kohara
authors.forename: Taiji
authors.initials: T
authors.lastname: Matsusaka
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
authors.forename: Pandelakis A
authors.initials: PA
authors.lastname: Koni
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kawada
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050199:Podocytes / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4