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Stromal cell-derived factor-1 (SDF1)-dependent recruitment of bone marrow-derived renal endothelium-like cells in a mouse model of acute kidney injury.

Ohnishi H, Mizuno S, Mizuno-Horikawa Y, Kato T - J. Vet. Med. Sci. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Blocking CXCR4 during AKI decreased engraftment of BM-derived ECs. (A) Anexperimental protocol of CXCR4 neutralization after renal I/R. (B) Inhibitory effectof CXCR4 blocking on CD31-positive BMC engraftment. Tissues were stained with CD31(red) and GFP (green), and the percentages of double positive cells (arrows) weremeasured. (C) Effect of CXCR4 neutralization on the differentiation of BMCs intoSMC-like cells. The percentages of cells double positive for α-SMA and GFP were shown.(D) Effect of CXCR4 neutralization on the improvement in renal tissue hypoxia. Hypoxicareas in OM region were measured by pimonidazole staining, and ratios ofpimonidazole-positive areas to total areas (×200) are shown. Data are shown as mean ±SD. **P<0.05 vs. normal IgG group. N.S., not significant.
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fig_004: Blocking CXCR4 during AKI decreased engraftment of BM-derived ECs. (A) Anexperimental protocol of CXCR4 neutralization after renal I/R. (B) Inhibitory effectof CXCR4 blocking on CD31-positive BMC engraftment. Tissues were stained with CD31(red) and GFP (green), and the percentages of double positive cells (arrows) weremeasured. (C) Effect of CXCR4 neutralization on the differentiation of BMCs intoSMC-like cells. The percentages of cells double positive for α-SMA and GFP were shown.(D) Effect of CXCR4 neutralization on the improvement in renal tissue hypoxia. Hypoxicareas in OM region were measured by pimonidazole staining, and ratios ofpimonidazole-positive areas to total areas (×200) are shown. Data are shown as mean ±SD. **P<0.05 vs. normal IgG group. N.S., not significant.

Mentions: Critical roles of SDF1-CXCR4 axis for BMCs to convert ECs during renalhypoxia: To test this hypothesis, mice were treated twice with an antibody todisrupt SDF1-CXCR4 signaling (Fig. 4AFig. 4.


Stromal cell-derived factor-1 (SDF1)-dependent recruitment of bone marrow-derived renal endothelium-like cells in a mouse model of acute kidney injury.

Ohnishi H, Mizuno S, Mizuno-Horikawa Y, Kato T - J. Vet. Med. Sci. (2015)

Blocking CXCR4 during AKI decreased engraftment of BM-derived ECs. (A) Anexperimental protocol of CXCR4 neutralization after renal I/R. (B) Inhibitory effectof CXCR4 blocking on CD31-positive BMC engraftment. Tissues were stained with CD31(red) and GFP (green), and the percentages of double positive cells (arrows) weremeasured. (C) Effect of CXCR4 neutralization on the differentiation of BMCs intoSMC-like cells. The percentages of cells double positive for α-SMA and GFP were shown.(D) Effect of CXCR4 neutralization on the improvement in renal tissue hypoxia. Hypoxicareas in OM region were measured by pimonidazole staining, and ratios ofpimonidazole-positive areas to total areas (×200) are shown. Data are shown as mean ±SD. **P<0.05 vs. normal IgG group. N.S., not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383777&req=5

fig_004: Blocking CXCR4 during AKI decreased engraftment of BM-derived ECs. (A) Anexperimental protocol of CXCR4 neutralization after renal I/R. (B) Inhibitory effectof CXCR4 blocking on CD31-positive BMC engraftment. Tissues were stained with CD31(red) and GFP (green), and the percentages of double positive cells (arrows) weremeasured. (C) Effect of CXCR4 neutralization on the differentiation of BMCs intoSMC-like cells. The percentages of cells double positive for α-SMA and GFP were shown.(D) Effect of CXCR4 neutralization on the improvement in renal tissue hypoxia. Hypoxicareas in OM region were measured by pimonidazole staining, and ratios ofpimonidazole-positive areas to total areas (×200) are shown. Data are shown as mean ±SD. **P<0.05 vs. normal IgG group. N.S., not significant.
Mentions: Critical roles of SDF1-CXCR4 axis for BMCs to convert ECs during renalhypoxia: To test this hypothesis, mice were treated twice with an antibody todisrupt SDF1-CXCR4 signaling (Fig. 4AFig. 4.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus