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

British Journal of Pharmacology
Tero A H Järvinen, Erkki Ruoslahti

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.

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Citations

Dec 14, 2018·British Journal of Pharmacology·James R WhitefordGiulia De Rossi
Apr 8, 2020·Journal of Cellular and Molecular Medicine·Kang YangFan Cheng
Feb 20, 2019·Journal of Cellular Physiology·Junyi HuZhaohui Chen
Dec 29, 2020·Frontiers in Endocrinology·Fuqiong ChenJiarong Tang
Jan 18, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Francis Migneault, Marie-Josée Hébert
Feb 15, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Magdalena SchneiderRudolf Fuchshofer
Oct 30, 2020·Frontiers in Immunology·Maja Wyczanska, Bärbel Lange-Sperandio
Dec 3, 2020·Frontiers in Immunology·Claire E McQuittyLuca Urbani
Jun 5, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Toini PemmariYanling Liao
Aug 10, 2021·World Journal of Clinical Oncology·Yun Zhu, Annie Lai Man Cheung

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