Work

Generation of a multi‐functional, target organ‐specific, anti‐fibrotic molecule by molecular engineering of the extracellular matrix protein, decorin

Year: 2018

Type: review

Abstract: Extracellular matrix (ECM) molecules play important roles in regulating processes such as cell proliferation, migration, differentiation and survival. Decorin is a proteoglycan that binds to ('decorates') collagen fibrils in the ECM. Decorin also interacts with many growth factors and their receptors, the most notable of these interactions being its inhibitory activity on TGF-β, the growth factor responsible for fibrosis formation. We have generated a recombinant, multi-functional, fusion-protein consisting of decorin as a therapeutic domain and a vascular homing and cell-penetrating peptide as a targeting vehicle. This recombinant decorin (CAR-DCN) accumulates at the sites of the targeted disease at higher levels and, as a result, has substantially enhanced biological activity over native decorin. CAR-DCN is an example of how molecular engineering can give a compound the ability to seek out sites of disease and enhance its therapeutic potential. CAR-DCN will hopefully be used to treat severe human diseases. LINKED ARTICLES: This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc.

Source: British Journal of Pharmacology

DOI: 10.1111/bph.14374

Authors: Tero A H Järvinen, Erkki Ruoslahti

Institutions: Tampere University, Tampere University Hospital, University of Tampere, Sanford Burnham Prebys Medical Discovery Institute

Language: English

Topic: TGF-β signaling in diseases

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Diabetes Research and Wellness Foundation, Academy of Finland, Päivikki ja Sakari Sohlbergin Säätiö, Tampereen Tuberkuloosisäätiö