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Development of stem cell derived type alveolar epithelial cells (AEC2s) for pulmonary fibrosis modeling

ABSTRACT: AEC2s are putatively major cells in development of lung diseases like Idiopathic Pulmonary Disease (IPF). For studying IPF-related phenotypes of AEC2s, We used differentiated AEC2s (diff-AEC2s) with some merits compared to conventional in vitro alveolar cells and bleomycin as a pulmonary fibrosis-inducing agent. With bleomycin treatment for 24 hr, some fibrotic phenotypes, senescent and transtional markers like Ctgf, Lgals3, and Krt8 were elevated with dose-dependent manner in RNA and protein expression. Also, up-regulation of P53 pathway and some irregular cell cycle expreesion were identified with bleomycin treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE284733 | GEO | 2025/01/02

REPOSITORIES: GEO

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Project description:Intratracheal application of bleomycin is known to induce inflammatory and fibrotic reactions in the lung within a short period of time and histological features include infiltration of inflammatory cells, collagen deposition and obliteration of alveolar spaces. Because some of these features are found in patients with idiopathic pulmonary fibrosis (IPF), the bleomycin-induced lung fibrosis animal model is commonly used. However, exploratory treatments that were successfully used in this animal model and progressed to clinical trials lacked significant efficacy in humans. Here, the bleomycin-induced rat lung fibrosis model was studied using whole genome expression data that was collected at various time points and the relevance to human disease was evaluated through comparison with whole genome expression data from IPF patient-derived lung biopsies. The highest gene expression correlation between both species was observed in animals 7 days after bleomycin instillation. These gene expression signatures helped to identify a set of twelve novel disease-relevant translational gene markers that were able to separate IPF patients from controls. Furthermore, three Wnt/-catenin pathway-related genes that belong to this translational gene marker set showed, together with clinical diffusing capacity of the lung for carbon monoxide (DLCO) measurements, the potential to stratify IPF patients according to disease severity. Pirfenidone attenuated a subset of the translational gene markers in the bleomycin-induced fibrosis model, in particular those related to Wnt/-catenin-signaling. This novel translational gene marker panel offers improved possibilities to evaluate disease-modifying efficacy of novel therapeutic concepts in the bleomycin-induced rat lung fibrosis model and could be applied as a diagnostic and prognostic tool for IPF patient care. Comparison of bleomycin-treated and control rats after 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks; 5 animals per group

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Development of stem cell derived type alveolar epithelial cells (AEC2s) for pulmonary fibrosis modeling

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