基质衍生因子-1-趋化因子受体 4/7 轴在体外脂肪组织间充质干细胞生物学行为中的作用。
The role of SDF-1-CXCR4/CXCR7 axis in biological behaviors of adipose tissue-derived mesenchymal stem cells in vitro.
机构信息
Plastic Surgery Department, Xuzhou Medical College Affiliated Hospital, Jiangsu, China.
出版信息
Biochem Biophys Res Commun. 2013 Nov 22;441(3):675-80. doi: 10.1016/j.bbrc.2013.10.071. Epub 2013 Oct 30.
Numerous studies have reported that CXCR4 and CXCR7 play an essential, but differential role in stromal cell-derived factor-1 (SDF-1)-inducing cell chemotaxis, viability and paracrine actions of BMSCs. Adipose tissue-derived mesenchymal stem cells (ADSCs) have been suggested to be potential seed cells for clinical application instead of bone marrow derived stroma cell (BMSCs). However, the function of SDF-1/CXCR4 and SDF-1/CXCR7 in ADSCs is not well understood. This study was designed to analyze the effect of SDF-1/CXCR4 and SDF-1/CXCR7 axis on ADSCs biological behaviors in vitro. Using Flow cytometry and Western blot methods, we found for the first time that CXCR4/CXCR7 expression was increased after treatment with SDF-1 in ADSCs. SDF-1 promoted ADSCs paracrine, proliferation and migration abilities. CXCR4 or CXCR7 antibody suppressed ADSCs paracrine action induced by SDF-1. The migration of ADSCs can be abolished by CXCR4 antibody, while the proliferation of ADSCs was only downregulated by CXCR7 antibody. Our study indicated that the angiogenesis of ADSCs is, at least partly, mediated by SDF-1/CXCR4 and SDF-1/CXCR7 axis. However, only binding of SDF-1/CXCR7 was required for proliferation of ADSCs, and CXCR7 was required for migration of ADSCs induced by SDF-1. Our studies provide evidence that the activation of either axis may be helpful to improve the effectiveness of ADSCs-based stem cell therapy.
大量研究报告称,趋化因子受体 4(CXCR4)和趋化因子受体 7(CXCR7)在基质细胞衍生因子-1(SDF-1)诱导细胞趋化、存活和旁分泌作用中发挥重要但不同的作用。脂肪组织来源的间充质干细胞(ADSCs)被认为是临床应用的潜在种子细胞,而不是骨髓来源的基质细胞(BMSCs)。然而,SDF-1/CXCR4 和 SDF-1/CXCR7 轴在 ADSCs 中的功能尚未完全阐明。本研究旨在分析 SDF-1/CXCR4 和 SDF-1/CXCR7 轴对 ADSCs 体外生物学行为的影响。通过流式细胞术和 Western blot 方法,我们首次发现 SDF-1 处理后 ADSCs 中 CXCR4/CXCR7 的表达增加。SDF-1 促进 ADSCs 的旁分泌、增殖和迁移能力。CXCR4 或 CXCR7 抗体抑制 SDF-1 诱导的 ADSCs 旁分泌作用。CXCR4 抗体可阻断 ADSCs 的迁移,而 CXCR7 抗体仅下调 SDF-1 诱导的 ADSCs 的增殖。我们的研究表明,ADSCs 的血管生成至少部分是由 SDF-1/CXCR4 和 SDF-1/CXCR7 轴介导的。然而,ADSCs 的增殖仅需要 SDF-1/CXCR7 的结合,而 SDF-1 诱导的 ADSCs 的迁移需要 CXCR7。我们的研究为激活任一轴可能有助于提高 ADSCs 基于干细胞治疗的有效性提供了证据。