Vimentin intermediate filament assembly regulates fibroblast invasion in fibrogenic lung injury

• DOI: 10.1172/jci.insight.123253
• Publication Date: 2019-04-03T17:41:59Z
• Authors: Ranu Surolia; Fu Jun Li; Zheng Wang; Huashi Li; Kevin Dsouza; Vinoy Thomas; Sergey Mirov; Dolores Pérez-Sala; Mohammad Athar; Victor J. Thannickal; Veena B. Antony
• Keywords: Myofibroblast

Idiopathic pulmonary fibrosis (IPF) is a progressive disease, with median survival of 3–5 years following diagnosis. Lung remodeling by invasive fibroblasts hallmark IPF. In this study, we demonstrate that inhibition vimentin intermediate filaments (VimIFs) decreases the invasiveness IPF and confers protection against in murine model experimental lung injury. Increased expression organization VimIFs contribute to property connection deficient cellular autophagy. Blocking VimIF assembly pharmacologic genetic means also increases autophagic clearance collagen type I. Furthermore, I siRNA decreased fibroblasts. bleomycin injury model, enhancing autophagy an inhibitor assembly, withaferin A (WFA), protected from fibrotic Additionally, 3D organoids, or pulmospheres, patients IPF, WFA reduced majority subjects tested. These studies provide insights into functional role vimentin, which regulates restricts