| First Author | Horejs CM | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15509 | PubMed ID | 28593951 |
| Mgi Jnum | J:249541 | Mgi Id | MGI:5921010 |
| Doi | 10.1038/ncomms15509 | Citation | Horejs CM, et al. (2017) Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information. Nat Commun 8:15509 |
| abstractText | 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 beta1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the beta1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor beta1 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. |
