The Matrix-Binding Domain of Microfibril-Associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix

Authors

  • Justin S. Weinbaum,

    Corresponding author
    1. Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, USA
    • Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, USA. Fax: (+1) 612 626 6583
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  • Robert T. Tranquillo,

    1. Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, USA
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  • Robert P. Mecham

    1. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
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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.

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