Yusuf Faisal, Rehimi Rizwan, Moroşan-Puopolo Gabriela, Dai Fangping, Zhang Xiaobing, Brand-Saberi Beate
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, Freiburg, Germany.
Dev Dyn. 2006 Nov;235(11):3007-15. doi: 10.1002/dvdy.20951.
Chemokines and their receptors play major roles in numerous physiological and pathological processes during development and disease. CXCR4 is the most abundantly expressed chemokine receptor during development. In contrast to other chemokine receptors, CXCR4 binds and is activated exclusively by its ligand stromal derived factor-1 (SDF-1) or CXCL12. SDF-1 signaling has a wide range of effects on CXCR4-expressing cells depending on the cell type ranging from cell growth to adhesion, chemotaxis, and migration. CXCR4 also serves as a co-receptor for HIV-1 entry into T-cells and has been implicated in the pathogenesis of rheumatoid arthritis and cancer growth and invasion. Numerous inhibitors and antagonists of CXCR4 have been produced and are being tested for their efficiency to target its role in pathogenesis. Our initial expression analysis revealed that CXCR4 is expressed by the migrating myogenic and angiogenic precursors in the developing chick limb. In this study, we used the most specific peptidic inhibitors of CXCR4, T140 and its analog TN14003, to analyse the effect of blocking CXCR4/SDF-1 signaling on the undetermined bioptent migratory progenitors in the developing chick limb. Our results point to defects in migration and an altered differentiation program of these CXCR4-expressing progenitor pool in the limb.
趋化因子及其受体在发育和疾病过程中的众多生理和病理过程中发挥着重要作用。CXCR4是发育过程中表达最为丰富的趋化因子受体。与其他趋化因子受体不同，CXCR4仅与它的配体基质细胞衍生因子-1（SDF-1）或CXCL12结合并被其激活。根据细胞类型的不同，SDF-1信号传导对表达CXCR4的细胞具有广泛的影响，范围从细胞生长到黏附、趋化性和迁移。CXCR4还是HIV-1进入T细胞的共受体，并与类风湿性关节炎以及癌症生长和侵袭的发病机制有关。目前已经产生了许多CXCR4的抑制剂和拮抗剂，并正在测试它们针对其在发病机制中作用的有效性。我们最初的表达分析表明，CXCR4在发育中的鸡胚肢体中迁移的生肌和血管生成前体细胞中表达。在本研究中，我们使用了最具特异性的CXCR4肽类抑制剂T140及其类似物TN14003，来分析阻断CXCR4/SDF-1信号传导对发育中的鸡胚肢体中未确定的双潜能迁移祖细胞的影响。我们的结果表明肢体中这些表达CXCR4的祖细胞库在迁移方面存在缺陷，并且分化程序发生了改变。
