Analysis of the Potential Relationship between Aging and Pulmonary Fibrosis Based on Transcriptome.

Abstract

Idiopathic pulmonary fibrosis (IPF) is an age-related interstitial lung disease with a high incidence in the elderly. Although many reports have shown that senescence can initiate pulmonary fibrosis, the relationship between aging and pulmonary fibrosis has not been explained systematically. In our study, young and old rats were intratracheally instilled with bleomycin (1 mg/kg), and the basic pathological indexes were determined using a commercial kit, hematoxylin, and eosin (H&E) and Masson's Trichrome staining, immunohistochemistry, immunohistofluorescence, and q-PCR. Then, the lung tissues of rats were sequenced by next-generation sequencing for transcriptome analysis. Bioinformatics was performed to analyze the possible differences in the mechanism of pulmonary fibrosis between aged and young rats. Finally, the related cytokines were determined by q-PCR and ELISA. The results indicate that pulmonary fibrosis in old rats is more serious than that in young rats under the same conditions. Additionally, transcriptomic and bioinformatics analysis with experimental validation indicate that the differences in pulmonary fibrosis between old and young rats are mainly related to the differential expression of cytokines, extracellular matrix (ECM), and other important signaling pathways. In conclusion, aging mainly affects pulmonary fibrosis through the ECM-receptor interaction, immune response, and chemokines.