Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information
Issue Date: 
2017
Publisher: 
Nature Research
ISSN: 
2041-1723
Note: 
CC BY
Citation: 
Horejs, C.M. (Christine-Maria); St-Pierre, J.P. (Jean-Philippe); Ojala, J.R.M. (Juha R. M.); et al. "Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information". Nature Communications. 8 (15509), 2017,
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 b1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the b1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor b1 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.

Files in This Item:
Thumbnail
File
Horejs CM, Stevens MM, 2017, NatCom.pdf
Description
Size
3.79 MB
Format
Adobe PDF


Statistics and impact

Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.