微纤维相关糖蛋白-1 的基质结合域将活性结缔组织生长因子靶向到成纤维细胞产生的细胞外基质。
The matrix-binding domain of microfibril-associated glycoprotein-1 targets active connective tissue growth factor to a fibroblast-produced extracellular matrix.
机构信息
Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, USA.
出版信息
Macromol Biosci. 2010 Nov 10;10(11):1338-44. doi: 10.1002/mabi.201000121.
Abstract
It is advantageous to use biomaterials in tissue engineering that stimulate extracellular matrix (ECM) production by the cellular component. Connective tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription, but is functionally limited as a free molecule. Using a matrix-binding domain (MBD) from microfibril-associated glycoprotein-1, the fusion protein MBD-CTGF was targeted to the ECM and tested for COL1A1 transcriptional activation. MBD-CTGF produced by the ECM-synthesizing fibroblasts, or provided exogenously, localized to the elastic fiber ECM. MBD-CTGF, but not CTGF alone, led to a two-fold enhancement of COL1A1 expression. This study introduces a targeting technology that can be used to elevate collagen transcription in engineered tissues and thereby improve tissue mechanics.
摘要
在组织工程中使用生物材料是有利的，这些生物材料可以刺激细胞成分产生细胞外基质 (ECM)。结缔组织生长因子 (CTGF) 可刺激 I 型胶原蛋白 (COL1A1) 的转录，但作为游离分子，其功能受到限制。利用微纤维相关糖蛋白 1 的基质结合结构域 (MBD)，将融合蛋白 MBD-CTGF 靶向 ECM，并测试其对 COL1A1 转录的激活作用。由合成细胞外基质的成纤维细胞产生的或外源性提供的 MBD-CTGF 定位于弹性纤维 ECM。MBD-CTGF 而非单独的 CTGF 可使 COL1A1 表达增加两倍。本研究介绍了一种靶向技术，可用于提高工程组织中的胶原蛋白转录水平，从而改善组织力学性能。
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