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.Evolution of the elastic fiber protein MAGP-1 has produced an intriguing solution to a common tissue engineering problem: how can a fully biological scaffold be created that can stimulate extracellular matrix production de novo? By tethering connective tissue growth factor to a cell-derived scaffold using a peptide derived from MAGP-1, Weinbaum et al. have created a completely biological biomaterial endowed with the ability to stimulate collagen production by fibroblasts.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1338-1344 |
| Number of pages | 7 |
| Journal | Macromolecular Bioscience |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 10 2010 |
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Keywords
- Biomaterials
- Extracellular matrix
- Fusion protein
- Growth factor
- Tissue engineering
Cite this
The Matrix-Binding Domain of Microfibril-Associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix. / Weinbaum, Justin S.; Tranquillo, Robert T; Mecham, Robert P.
In: Macromolecular Bioscience, Vol. 10, No. 11, 10.11.2010, p. 1338-1344.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Matrix-Binding Domain of Microfibril-Associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix
AU - Weinbaum, Justin S.
AU - Tranquillo, Robert T
AU - Mecham, Robert P.
PY - 2010/11/10
Y1 - 2010/11/10
N2 - 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.Evolution of the elastic fiber protein MAGP-1 has produced an intriguing solution to a common tissue engineering problem: how can a fully biological scaffold be created that can stimulate extracellular matrix production de novo? By tethering connective tissue growth factor to a cell-derived scaffold using a peptide derived from MAGP-1, Weinbaum et al. have created a completely biological biomaterial endowed with the ability to stimulate collagen production by fibroblasts.
AB - 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.Evolution of the elastic fiber protein MAGP-1 has produced an intriguing solution to a common tissue engineering problem: how can a fully biological scaffold be created that can stimulate extracellular matrix production de novo? By tethering connective tissue growth factor to a cell-derived scaffold using a peptide derived from MAGP-1, Weinbaum et al. have created a completely biological biomaterial endowed with the ability to stimulate collagen production by fibroblasts.
KW - Biomaterials
KW - Extracellular matrix
KW - Fusion protein
KW - Growth factor
KW - Tissue engineering
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U2 - 10.1002/mabi.201000121
DO - 10.1002/mabi.201000121
M3 - Article
VL - 10
SP - 1338
EP - 1344
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
SN - 1616-5187
IS - 11
ER -