Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information
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Published version
OA Location
Author(s)
Type
Journal Article
Abstract
Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets.
Date Issued
2017-06-08
Date Acceptance
2017-04-04
Citation
Nature Communications, 2017, 8
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
8
Copyright Statement
© 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Commission of the European Communities
Commission of the European Communities
Grant Number
MR/L012677/1
MR/K026682/1
ERC-2013-CoG-616417
PIEF-GA-2013-625472
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
TO-MESENCHYMAL TRANSITION
GROWTH-FACTOR-BETA
ENCAPSULATING PERITONEAL SCLEROSIS
MEMBRANE TRANSMIGRATION PROGRAM
BASEMENT-MEMBRANE
SURFACE FUNCTIONALIZATION
ELECTROSPUN NANOFIBERS
PULMONARY-FIBROSIS
MESOTHELIAL CELLS
RENAL FIBROSIS
MD Multidisciplinary
Publication Status
Published
Article Number
15509