PLK1 Inhibition alleviates transplant-associated obliterative bronchiolitis by suppressing myofibroblast differentiation.

ABSTRACT: Chronic allograft dysfunction (CAD) resulting from fibrosis is the major limiting factor for long-term survival of lung transplant patients. Myofibroblasts promote fibrosis in multiple organs, including the lungs. In this study, we identified PLK1 as a promoter of myofibroblast differentiation and investigated the mechanism by which its inhibition alleviates transplant-associated obliterative bronchiolitis (OB) during CAD. High-throughput bioinformatic analyses and experiments using the murine heterotopic tracheal transplantation model revealed that PLK1 is upregulated in grafts undergoing CAD as compared with controls, and that inhibiting PLK1 alleviates OB in vivo. Inhibition of PLK1 in vitro reduced expression of the specific myofibroblast differentiation marker α-smooth m

SUBMITTER: Yu J 

PROVIDER: S-EPMC7343459 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature