Hollier Brett, Harkin Damien G, Leavesley David, Upton Zee
Tissue BioRegeneration and Integration Program, Science Research Centre, School of Life Sciences, Queensland University of Technology, GPO Box 2434, Brisbane, Queensland 4001, Australia.
Exp Cell Res. 2005 Apr 15;305(1):221-32. doi: 10.1016/j.yexcr.2005.01.004.
Insulin-like growth factor-1 (IGF-I) can associate with the extracellular matrix protein vitronectin (VN) via select IGF-binding proteins, and the resulting complex stimulates responses in a variety of cell types. As VN can also associate with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), we hypothesized that the multimeric nature of VN could be exploited to deliver multiple growth factors to the cell surface. We report here that VN enhances bFGF but not EGF stimulated [(3)H]-leucine incorporation in the HaCAT keratinocyte cell line, with VN synergistically enhancing cell migration in response to both EGF and bFGF when presented as a VN-bound complex. Furthermore, the addition of EGF and/or bFGF to IGF-I:IGFBP-5:VN complexes significantly enhances both [(3)H]-leucine incorporation and migration of HaCAT cells above that induced by IGF:IGFBP-5:VN complexes alone. Indeed, similar responses are observed in primary cultures of human skin keratinocytes, highlighting the potential use of these novel complexes for a wide range of tissue repair applications.
胰岛素样生长因子-1（IGF-I）可通过特定的胰岛素样生长因子结合蛋白与细胞外基质蛋白玻连蛋白（VN）结合，形成的复合物可刺激多种细胞类型产生反应。由于VN还可与表皮生长因子（EGF）和碱性成纤维细胞生长因子（bFGF）结合，我们推测VN的多聚体性质可用于将多种生长因子递送至细胞表面。我们在此报告，VN可增强bFGF刺激的HaCAT角质形成细胞系中[³H]-亮氨酸掺入，但不增强EGF刺激的[³H]-亮氨酸掺入，当以VN结合复合物形式存在时，VN可协同增强细胞对EGF和bFGF的迁移反应。此外，向IGF-I:IGFBP-5:VN复合物中添加EGF和/或bFGF，可显著增强HaCAT细胞的[³H]-亮氨酸掺入和迁移，其增强程度高于单独的IGF:IGFBP-5:VN复合物诱导的水平。实际上，在人皮肤角质形成细胞原代培养中也观察到了类似的反应，这突出了这些新型复合物在广泛的组织修复应用中的潜在用途。
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