Simultaneously Targeting Myofibroblast Contractility and Extracellular Matrix Cross-Linking as a Therapeutic Concept in Airway Fibrosis.

ABSTRACT: Fibrosis after solid organ transplantation is considered an irreversible process and remains the major cause of graft dysfunction and death with limited therapies. This remodeling is characterized by aberrant accumulation of contractile myofibroblasts that deposit excessive extracellular matrix (ECM) and increase tissue stiffness. Studies demonstrate, however, that a stiff ECM itself promotes fibroblast-to-myofibroblast differentiation, stimulating further ECM production. This creates a positive feedback loop that perpetuates fibrosis. We hypothesized that simultaneously targeting myofibroblast contractility with relaxin and ECM stiffness with lysyl oxidase inhibitors could break the feedback loop, reversing established fibrosis. To test this, we used the orthotopic tracheal transplantatio

SUBMITTER: Lin YC 

PROVIDER: S-EPMC5409855 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature