Extracellular calcium increases CXCR4 expression on bone marrow-derived cells and enhances pro-angiogenesis therapy
Quiling Wu
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorHongwei Shao
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorVascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Division of Vascular Surgery, Miami Veterans Affair, Miami, FL, USA
Search for more papers by this authorJiahui Li
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorJie Li
Department of Dermatology, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorBing Yang
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorKeith A. Webster
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorCorresponding Author
Hong Yu
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Division of Vascular Surgery, Miami Veterans Affair, Miami, FL, USA
Correspondence to: Hong YU, Ph.D., Vascular Biology Institute, University of Miami School of Medicine, 1600 NW, 10th Avenue, RMSB 7139, Miami, FL 33136, USA.Tel.: (305) 575-7000 (ext 3998)Fax: (305) 575-3126E-mail: [email protected]Search for more papers by this authorQuiling Wu
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorHongwei Shao
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorVascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Division of Vascular Surgery, Miami Veterans Affair, Miami, FL, USA
Search for more papers by this authorJiahui Li
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorJie Li
Department of Dermatology, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorBing Yang
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorKeith A. Webster
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorCorresponding Author
Hong Yu
Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
Division of Vascular Surgery, Miami Veterans Affair, Miami, FL, USA
Correspondence to: Hong YU, Ph.D., Vascular Biology Institute, University of Miami School of Medicine, 1600 NW, 10th Avenue, RMSB 7139, Miami, FL 33136, USA.Tel.: (305) 575-7000 (ext 3998)Fax: (305) 575-3126E-mail: [email protected]Search for more papers by this authorAbstract
Cell surface receptors play major roles in the mobilization and homing of progenitor cells from the bone marrow to peripheral tissues. CXCR4 is an important receptor that regulates homing of leucocytes and endothelial progenitors in response to the chemokine stromal cell-derived factor-1 (SDF-1). Ionic calcium is also known to regulate chemotaxis of selective bone marrow cells (BMCs) through the calcium-sensing receptor, CaR. Here we show that calcium regulates CXCR4 expression and BMC responses to SDF-1. CaCl2 treatment of BMC induced a time- and dose-dependent increase in both the transcription and cell surface expression of CXCR4. BMC subpopulations expressing VEGFR2+, CD34+ and cKit+/Sca-1+ were especially sensitive to calcium. The effects were blocked by calcium influx inhibitors, anti-CaR antibody and the protein synthesis inhibitor cycloheximide, but not by the CXCR4 antagonist AMD3100. Calcium treatment also enhanced SDF-1-mediated CXCR4 internalization. These changes were reflected in significantly improved chemotaxis by SDF-1, which was abolished by AMD3100 and by antibody against CXCR4. Calcium pre-treatment improved homing of CD34+ BMCs to ischemic muscle in vivo, and enhanced revascularization in ischemic mouse hindlimbs. Our results identify calcium as a positive regulator of CXCR4 expression that promotes stem cell mobilization, homing and therapy.
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