Blockade of CXC chemokine receptor-4 improves hepatocyte proliferation after ischemia/reperfusion in a murine model (144.2)

Stromal-cell derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), have been shown to contribute to stem cell mobilization and angiogenesis and therefore may be important mediators of regenerative processes. In the current study, we examined whether the SDF-1/CXCR4 system was involved in liver regeneration after ischemia/reperfusion (I/R) injury. A murine model of partial I/R was used to induce liver injury and study the regenerative response. CXCR4 antagonist (AMD3100) or agonist (SDF-1) was administered to some mice. Serum alanine aminotransferase (ALT) and liver myeloperoxidase (MPO) content were used to assess liver injury and inflammation. Proliferating cell nuclear antigen (PCNA) staining was used to assess hepatocyte proliferation. Hepatic expression of CXCR4 was determined by western blot and serum SDF-1 was measured by ELISA. CXCR4 was expressed constitutively in the liver and SDF-1 levels in serum peaked at 8 hours of reperfusion and returned to baseline by 24 hours. CXCR4...