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https://www.selleckchem.com/products/ko143.html Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease whose underlying mechanisms have been primarily investigated in mice after intratracheal instillation of a single dose of bleomycin. However, the model has significant limitations including the transient fibrosis which spontaneously resolves and its failure to fully recapitulate the epithelial remodeling in the lungs of IPF patients. Thus, there remains an unmet need for a pre-clinical model with features that more closely resemble the human disease. Repetitive intratracheal instillation of bleomycin has previously been shown to recapitulate some of these features, but the instillation procedure is complex and the long-term consequences on epithelial remodeling and fibrosis persistence and progression remain poorly understood. Here, we developed a simplified repetitive bleomycin instillation strategy consisting of three bi-weekly instillations that leads to persistent and progressive pulmonary fibrosis. Lung histology demonstrates increased collagen deposition, fibroblast accumulation, loss of type I and type II alveolar epithelial cells (AEC1s and AEC2s) within fibrotic areas, bronchiolization of the lung parenchyma with CCSP+ cells, remodeling of the distal lung into cysts reminiscent of simple honeycombing, and the accumulation of hyperplastic transitional KRT8+ epithelial cells. MicroCT imaging demonstrated significant traction bronchiectasis and subpleural fibrosis. Thus, the simplified repetitive bleomycin instillation strategy leads to progressive fibrosis and recapitulates the histological and radiographic characteristics of IPF. Compared to the single bleomycin instillation model, we suggest that the simplified repetitive instillation model

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