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

Justin S. Weinbaum, Robert T Tranquillo, Robert P. Mecham

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1338-1344
Number of pages7
JournalMacromolecular Bioscience
Volume10
Issue number11
DOIs
StatePublished - Nov 10 2010

Fingerprint

Connective Tissue Growth Factor
Glycoproteins
Fibroblasts
Extracellular Matrix
Tissue
Elastic Tissue
Collagen
Biocompatible Materials
Transcription
Tissue Engineering
Tissue engineering
Scaffolds
Biomaterials
Fibers
Collagen Type I
Mechanics
Proteins
Protein Binding
Transcriptional Activation
microfibrillar protein

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 journalArticle

@article{0d64dc70d8d34e01967ebd7865663903,
title = "The Matrix-Binding Domain of Microfibril-Associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix",
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.",
keywords = "Biomaterials, Extracellular matrix, Fusion protein, Growth factor, Tissue engineering",
author = "Weinbaum, {Justin S.} and Tranquillo, {Robert T} and Mecham, {Robert P.}",
year = "2010",
month = "11",
day = "10",
doi = "10.1002/mabi.201000121",
language = "English (US)",
volume = "10",
pages = "1338--1344",
journal = "Macromolecular Bioscience",
issn = "1616-5187",
publisher = "Wiley-VCH Verlag",
number = "11",

}

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

UR - http://www.scopus.com/inward/record.url?scp=78650891503&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650891503&partnerID=8YFLogxK

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 -