Yu Lan, Cecil Jeffrey, Peng Sheng-Bin, Schrementi James, Kovacevic Steven, Paul Donald, Su Eric Wen, Wang Jian
Cardiovascular Division, Lilly Research Laboratories, Eli Lilly and Company, DC0434, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Gene. 2006 Jun 7;374:174-9. doi: 10.1016/j.gene.2006.02.001. Epub 2006 Apr 19.
Stromal Cell-derived factor 1 (SDF-1) is a CXC chemokine that binds to the CXCR4 receptor. Recent publication indicates that the SDF-1/CXCR4 signaling pathway plays a pivotal role during development and in many patho-physiological conditions including hematopoiesis, blood vessel formation, cancer metastasis, angiogenesis and HIV infection. Two human SDF-1 isoforms, SDF-1alpha and SDF-1beta, have been reported to date. Here we report the identification of four additional human SDF-1 isoforms derived from alternative splicing events, SDF-1gamma, SDF-1delta, SDF-1epsilon and SDF-1phi. These SDF-1 splice variants all share the same first three exons but contain different fourth exons. The human SDF-1 gene spans over 88 kilobase-pairs on chromosome 10. Using the semi-quantitative RT-PCR method, we determined the tissue distribution of these SDF-1 isoforms. SDF-1alpha and SDF-1beta share similar expression patterns and the highest expression were detected in liver, pancreas and spleen. SDF-1gamma seems to be the human orthologue of recently isolated rat SDF-1gamma, and its expression was only detected in the heart. SDF-1delta expression can be detected in several adult tissues but the highest expression was detected in fetal liver. When transfected into HEK293 cells, all the SDF-1 isoforms can be detected as secreted proteins in the cell culture media. The conditioned media from transfected cells can stimulate cell migration in a CXCR4-dependent manner. These data suggest that the novel SDF-1 splice variants encode functional proteins.
基质细胞衍生因子1（SDF-1）是一种与CXCR4受体结合的CXC趋化因子。最近的研究表明，SDF-1/CXCR4信号通路在发育过程以及包括造血、血管形成、癌症转移、血管生成和HIV感染在内的许多病理生理状况中发挥着关键作用。迄今为止，已报道了两种人类SDF-1亚型，即SDF-1α和SDF-1β。在此，我们报告了另外四种源自可变剪接事件的人类SDF-1亚型的鉴定，即SDF-1γ、SDF-1δ、SDF-1ε和SDF-1φ。这些SDF-1剪接变体均共享相同的前三个外显子，但包含不同的第四个外显子。人类SDF-1基因在10号染色体上跨度超过88千碱基对。使用半定量RT-PCR方法，我们确定了这些SDF-1亚型的组织分布。SDF-1α和SDF-1β具有相似的表达模式，在肝脏、胰腺和脾脏中检测到最高表达。SDF-1γ似乎是最近分离出的大鼠SDF-1γ的人类同源物，其表达仅在心脏中检测到。SDF-1δ的表达可在几种成人组织中检测到，但在胎儿肝脏中检测到最高表达。当转染到HEK293细胞中时，所有SDF-1亚型均可在细胞培养基中作为分泌蛋白被检测到。转染细胞的条件培养基可以以CXCR4依赖的方式刺激细胞迁移。这些数据表明，新型SDF-1剪接变体编码功能性蛋白质。
