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

• Published in: Nature communications Vol. 8; no. 1; p. 15509
• Main Authors: Horejs, Christine-Maria, St-Pierre, Jean-Philippe, Ojala, Juha R. M., Steele, Joseph A. M., da Silva, Patricia Barros, Rynne-Vidal, Angela, Maynard, Stephanie A., Hansel, Catherine S., Rodríguez-Fernández, Clara, Mazo, Manuel M., You, Amanda Y. F., Wang, Alex J., von Erlach, Thomas, Tryggvason, Karl, López-Cabrera, Manuel, Stevens, Molly M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-06-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 13/107; 639/166/985; 639/301/54/2295; 64; 64/60; 82; 82/1; 82/51; 96; Animals; Biocompatible Materials - chemistry; Bioengineering; Biomedical materials; Disease Models, Animal; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition - genetics; Epithelium - metabolism; Extracellular matrix; Extracellular Matrix - metabolism; Fairs & exhibitions; Gene Expression Profiling; HEK293 Cells; Humanities and Social Sciences; Humans; Integrin alpha3beta1 - metabolism; Laminin - metabolism; Mammary Glands, Human - cytology; Matrix Metalloproteinase 2 - metabolism; Medicin och hälsovetenskap; Membranes, Artificial; Mice; multidisciplinary; Peritoneal Fibrosis - metabolism; Peritoneal Fibrosis - pathology; Peritoneum - metabolism; Protein Binding; Science; Science (multidisciplinary); Signal Transduction; Stem cells; United Kingdom > UK; Singapore
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15509

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.
Matrix metalloproteinase enzymes are widely known to contribute to the breakdown of tissues. Here, the authors utilise a biomaterial substrate functionalised with a laminin fragment to modulate the expression of these enzymes, subsequently controlling the integrity of tissue.