title: Stromal cell-derived factor-1 (SDF1)-dependent recruitment of bone marrow-derived renal endothelium-like cells in a mouse model of acute kidney injury.
abstract: Ischemic acute kidney injury (AKI) is the most key pathological event for accelerating progression to chronic kidney disease through vascular endothelial injury or dysfunction. Thus, it is critical to elucidate the molecular mechanism of endothelial protection and regeneration. Emerging evidence indicates that bone marrow-derived cells (BMCs) contribute to tissue reconstitution in several types of organs post-injury, but little is known whether and how BMCs contribute to renal endothelial reconstitution, especially in an early-stage of AKI. Using a mouse model of ischemic AKI, we provide evidence that incorporation of BMCs in vascular components (such as endothelial and smooth muscle cells) becomes evident within four days after renal ischemia and reperfusion, associated with an increase in stromal cell-derived factor-1 (SDF1) in endothelium and that in CXCR4/SDF1-receptor in BMCs. Notably, anti-CXCR4 antibody decreased the numbers of infiltrated BMCs and BMC-derived endothelium-like cells, but not of BMC-derived smooth muscle cell-like cells. These results suggest that reconstitution of renal endothelium post-ischemia partially depends on a paracrine loop of SDF1-CXCR4 between resident endothelium and BMCs. Such a chemokine ligand-receptor system may be attributable for selecting a cellular lineage (s), required for renal vascular protection, repair and homeostasis, even in an earlier phase of AKI.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School of Medicine, 2–2 Yamadaoka, Suita 565–0871; 2. Kinjo Gakuin University College of Pharmacy, 2-1723 Oomori, Moriyama-ku, Nagoya 463-8521, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Shinya
authors.initials: S
authors.lastname: Mizuno
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizuno-Horikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019899:Paracrine Communication / Q000502:physiology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins
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