Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information

Christine-Maria Horejs (), Jean-Philippe St-Pierre, Juha R. M. Ojala, Joseph A. M. Steele, Patricia Barros da Silva, Angela Rynne-Vidal, Stephanie A. Maynard, Catherine S. Hansel, Clara Rodríguez-Fernández, Manuel M. Mazo, Amanda Y. F. You, Alex J. Wang, Thomas von Erlach, Karl Tryggvason, Manuel López-Cabrera and Molly M. Stevens ()
Additional contact information
Christine-Maria Horejs: Imperial College London
Jean-Philippe St-Pierre: Imperial College London
Juha R. M. Ojala: Karolinska Institutet
Joseph A. M. Steele: Imperial College London
Patricia Barros da Silva: Karolinska Institutet
Angela Rynne-Vidal: Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco
Stephanie A. Maynard: Imperial College London
Catherine S. Hansel: Imperial College London
Clara Rodríguez-Fernández: Imperial College London
Manuel M. Mazo: Imperial College London
Amanda Y. F. You: Imperial College London
Alex J. Wang: Imperial College London
Thomas von Erlach: Imperial College London
Karl Tryggvason: Karolinska Institutet
Manuel López-Cabrera: Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco
Molly M. Stevens: Imperial College London

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15509 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15509

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15509

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().