Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease that is caused by the dysregulation of alveolar epithelial type II cells (AEC II). The mechanisms involved in the progression of IPF remain incompletely understood, although the immune response accompanied by p38 mitogen-activated protein kinase (MAPK) activation may contribute to some of them. This study aimed to examine the association of p38 activity in the lungs with bleomycin (BLM)-induced pulmonary fibrosis and its transcriptomic profiling. Accordingly, we evaluated BLM-induced pulmonary fibrosis during an active fibrosis phase in three genotypes of mice carrying stepwise variations in intrinsic p38 activity in the AEC II and performed RNA sequencing of their lungs. Stepwise elevation of p38 signaling in the lungs of the three genotypes was correlated with increased severity of BLM-induced pulmonary fibrosis exhibiting reduced static compliance and higher collagen content. Transcriptome analysis of these lung samples also showed that the enhanced p38 signaling in the lungs was associated with increased transcription of the genes driving the p38 MAPK pathway and differentially expressed genes elicited by BLM, including those related to fibrosis as well as the immune system. Our findings underscore the significance of p38 MAPK in the progression of pulmonary fibrosis.
Highlights
Pulmonary fibrosis is the result of the end-stage pathological development of existing lung diseases caused by infection, autoimmunity, chronic inflammation, and idiopathy
Recent studies focusing on the behaviors of extracellular matrix (ECM)-producing myofibroblasts in pulmonary fibrosis may inform the identification of therapeutic options for Idiopathic pulmonary fibrosis (IPF) [5,6,7,8]
The distinct severity of pulmonary fibrosis was evident in semi-quantitative evaluation assessed by a modified Ashcroft score and stratified by three mouse groups
Summary
Pulmonary fibrosis is the result of the end-stage pathological development of existing lung diseases caused by infection, autoimmunity, chronic inflammation, and idiopathy. Idiopathic pulmonary fibrosis (IPF), one of the most common causes of interstitial pneumonia, is characterized by progressive and irreversible fibrotic scar formation in the gas exchange regions of the lung, resulting in organ malfunction. Innate and adaptive inflammation may contribute to determining the rate of disease progression in patients with IPF [3]. The mortality of patients with IPF is correlated with the extent of fibrotic focus formation, which results from the abnormal and excessive accumulation of extracellular matrix (ECM) components, including collagen, fibronectin, and elastin [4]. New beneficial strategies that enable patients with IPF to survive longer and with improved quality of life have been long-awaited
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