Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7

作者：Sierro Frederic; Biben Christine; Martinez Munoz Laura; Mellado Mario; Ransohoff Richard M; Li Meizhang; Woehl Blanche; Leung Helen; Groom Joanna; Batten Marcel; Harvey Richard P; Martinez A Carlos; Mackay Charles R; Mackay Fabienne^*

来源：Proceedings of the National Academy of Sciences, 2007, 104(37): 14759-14764.

DOI：10.1073/pnas.0702229104

• chemokines
• heart
• heterodimerization
• immunology
• endothelium

Chemotactic cytokines (chemokines) attract immune cells, although their original evolutionary role may relate more closely with embryonic development. We noted differential expression of the chemokine receptor CXCR7 (RDC-1) on marginal zone B cells, a cell type associated with autoimmune diseases. We generated Cxcr7(-1-) mice but found that CXCR7 deficiency had little effect on B cell composition. However, most Cxcr7-1- mice died at birth with ventricular septal defects and semilunar heart valve malformation. Conditional deletion of Cxcr7 in endothelium, using Tie2-Cre trans-genic mice, recapitulated this phenotype. Gene profiling of Cxcr7-1- heart valve leaflets revealed a defect in the expression of factors essential for valve formation, vessel protection, or endothelial cell growth and survival. We confirmed that the principal chemokine ligand for CXCR7 was CXCL12/SDF-1, which also binds CXCR4. CXCL12 did not induce signaling through CXCR7; however, CXCR7 formed functional heterodimers with CXCR4 and enhanced CXCL12-induced signaling. Our results reveal a specialized role for CXCR7 in endothelial biology and valve development and highlight the distinct developmental role of evolutionary conserved chemokine receptors such as CXCR7 and CXCR4.

• 出版日期2007-9-11
• 单位河北医科大学