Deficiency of either P-glycoprotein or breast cancer resistance protein protect against acute kidney injury.
SourceCell Transplantation, 19, 9, (2010), pp. 1195-1208
Article / Letter to editor
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Laboratory of Hematology
IMM - Institute for Molecules and Materials
SubjectIGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 9: Renal disorder; NCMLS 2: Immune Regulation; NCMLS 5: Membrane transport and intracellular motility; ONCOL 3: Translational research; Synthetic Organic Chemistry
The kidney has a high capacity to regenerate after ischemic injury via several mechanisms, one of which involves bone marrow-derived (stem) cells. The ATP binding cassette transporters, P-glycoprotein and breast cancer resistance protein, are determinants for the enriched stem and progenitor cell fraction in bone marrow. Because they are upregulated after acute kidney injury, we hypothesized that both efflux pumps may play a role in protecting against renal injury. Surprisingly, transporter-deficient mice were protected against ischemia-induced renal injury. To further study this, bone marrow from irradiated wild-type mice was reconstituted by bone marrow from wild-type, P-glycoprotein- or breast cancer resistance protein-deficient mice. Four weeks later, kidney injury was induced and its function evaluated. Significantly more bone marrow-derived cells were detected in kidneys grafted with transporter-deficient bone marrow. A gender mismatch study suggested that cell fusion of resident tubular cells with bone marrow cells was unlikely. Renal function analyses indicated an absence of renal damage following ischemia-reperfusion in animals transplanted with transporter-deficient bone marrow. When wild-type bone marrow was transplanted in breast cancer resistance protein-deficient mice this protection is lost. Furthermore, we demonstrate that transporter-deficient bone marrow contained significantly more monocytes, granulocytes, and early outgrowth endothelial progenitor cells.
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