CXC-chemokine receptor 4 antagonist prevents acute kidney injury potentially through recruiting bone marrow-derived stem cells

Abstract

Background: Existing literature suggests that stromal-cell derived factor 1 (SDF-1) interacts with CXC-chemokine receptor 4 (CXCR4) in regulating the homing of stem cells derived from bone marrow. The CXCR4 antagonist, AMD3100, disrupts this SDF-1/CXCR4 interaction and triggers stem cell mobilization. We investigated whether AMD3100 could ameliorate renal ischemia reperfusion (I/R) injury via recruiting circulating stem cells to injured kidneys. Methods: We divided Sprague-Dawley rats into four groups, Sham, Sham + AMD3100, I/R, and I/R + AMD3100. All groups were treated with single subcutaneous injections of AMD3100 (5 mg/kg) or saline after sham surgery or I/R injury. Serum and renal tissues were harvested 12 hours and 3 days after treatment. We assessed survival, renal function changes, and histopathological alterations. TUNEL staining and caspase-3 expression levels were harnessed to measure tubular cell apoptosis, and circulating CXCR4 and CD34 positive mononuclear cells were identified by flow cytometry. Results: The I/R + AMD3100 group displayed significantly higher survival, lower serum creatinine, less prominent renal damage upon histopathological examination, and a lower degree of apoptosis than the I/R group. In addition, the AMD3100 treated group showed a significantly higher degree of CXCR4 and CD34 positive cell mobilization in the circulation and increased recruitment of these cells into the injured kidneys. Conclusions: AMD3100 promotes bone marrow stem cell mobilization and improves the recovery of renal function after I/R injury, and this effect may offer a promising therapeutic approach for acute kidney injury.