volasertib and Fibrosis

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

Topics: Actins; Allografts; Animals; Bronchiolitis Obliterans; Cell Cycle Proteins; Cell Differentiation; Cells, Cultured; Chronic Disease; Computational Biology; Disease Models, Animal; Fibrosis; Gene Knockdown Techniques; Graft Rejection; Healthy Volunteers; Humans; Lung; Lung Transplantation; Male; MAP Kinase Signaling System; Mice; Myofibroblasts; NIH 3T3 Cells; Pentose Phosphate Pathway; Phosphorylation; Polo-Like Kinase 1; Primary Cell Culture; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Pteridines; RNA-Seq; Trachea; Transforming Growth Factor beta1; Up-Regulation