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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

Up-regulation of SDF1 and appearance of BMCs expressing CXCR4 during AKI. (A)Expressions of SDF1 mRNA (left) and protein (right) in the ischemic kidney weremeasured by real-time PCR and ELISA, respectively. (B) Localization of SDF1 expression(red) was detected by immunohistochemistry. (C) Double immunostaining of SDF1 (red)and CD31 (upper panel, green) or Na+-K+-ATPase (lower panel,green) in the kidney after renal I/R. (D) BMCs (green) positive for CXCR4immunostaining (red) were detected in the kidney after renal I/R (arrows). Data areshown as mean ± SD.
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fig_003: Up-regulation of SDF1 and appearance of BMCs expressing CXCR4 during AKI. (A)Expressions of SDF1 mRNA (left) and protein (right) in the ischemic kidney weremeasured by real-time PCR and ELISA, respectively. (B) Localization of SDF1 expression(red) was detected by immunohistochemistry. (C) Double immunostaining of SDF1 (red)and CD31 (upper panel, green) or Na+-K+-ATPase (lower panel,green) in the kidney after renal I/R. (D) BMCs (green) positive for CXCR4immunostaining (red) were detected in the kidney after renal I/R (arrows). Data areshown as mean ± SD.

Mentions: Hypoxia-associated up-regulation of SDF1 in ECs and of CXCR4 in BMCs:Growing evidence suggests that SDF1 is a key chemokine to elicit engraftment of BMCs intohypoxic organs or tissues [5, 31]. In our model, mRNA and protein levels of SDF1 dramatically raised 2days post-challenge and then returned near the basal levels at 6 days post-renal I/R (Fig. 3AFig. 3.


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)

Up-regulation of SDF1 and appearance of BMCs expressing CXCR4 during AKI. (A)Expressions of SDF1 mRNA (left) and protein (right) in the ischemic kidney weremeasured by real-time PCR and ELISA, respectively. (B) Localization of SDF1 expression(red) was detected by immunohistochemistry. (C) Double immunostaining of SDF1 (red)and CD31 (upper panel, green) or Na+-K+-ATPase (lower panel,green) in the kidney after renal I/R. (D) BMCs (green) positive for CXCR4immunostaining (red) were detected in the kidney after renal I/R (arrows). Data areshown as mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig_003: Up-regulation of SDF1 and appearance of BMCs expressing CXCR4 during AKI. (A)Expressions of SDF1 mRNA (left) and protein (right) in the ischemic kidney weremeasured by real-time PCR and ELISA, respectively. (B) Localization of SDF1 expression(red) was detected by immunohistochemistry. (C) Double immunostaining of SDF1 (red)and CD31 (upper panel, green) or Na+-K+-ATPase (lower panel,green) in the kidney after renal I/R. (D) BMCs (green) positive for CXCR4immunostaining (red) were detected in the kidney after renal I/R (arrows). Data areshown as mean ± SD.
Mentions: Hypoxia-associated up-regulation of SDF1 in ECs and of CXCR4 in BMCs:Growing evidence suggests that SDF1 is a key chemokine to elicit engraftment of BMCs intohypoxic organs or tissues [5, 31]. In our model, mRNA and protein levels of SDF1 dramatically raised 2days post-challenge and then returned near the basal levels at 6 days post-renal I/R (Fig. 3AFig. 3.

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