Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice

TL;DR

This study shows that autophagy activity decreases as pulmonary fibrosis worsens in mice, suggesting a link between autophagy and lung tissue damage.

Contribution

The study reveals a dose-dependent relationship between bleomycin-induced pulmonary fibrosis and reduced autophagy activity in mice.

Findings

Bleomycin increased fibrosis markers and decreased autophagy-related gene and protein expressions in a dose-dependent manner.

Autophagy activity was inversely correlated with the severity of pulmonary fibrosis in mice.

LC3II/LC3I and Atg gene expressions were significantly reduced in fibrotic lung tissues.

Abstract

The aim of this study is to observe the changes in autophagy activities in lung tissues of mice with different degrees of pulmonary fibrosis (PF), and explore the association between PF and autophagy activity. The PF model was established by bleomycin (BLM, 25 and 35 mg/kg) atomization inhalation in C57BL/6 mice, samples were collected on the 7, 14, and 28 days after BLM administration. Hematoxylin–eosin staining was used to observe the pathological changes in lung tissues. Masson staining was utilized to assess areas of blue collagen fiber deposition in lung tissues. Quantitative real time polymerase chain reaction was used to detect the mRNA expressions of autophagy-related genes, including Atg5, Atg7, and Atg10 in lung tissues. Western blot was used to detect the protein expressions of autophagy-related genes, including p62 and LC3II/LC3I in lung tissues. Compared with control group, BLM dose-dependently decreased PaO2, mRNA expressions of Atg5, Atg7, Atg10, and LC3II/LC3I, while increased lung wet weight, lung coefficient, PF score, the blue area of collagen fibers, and p62 protein on the 7th, 14th, and 28th days. In conclusion, the more severe the PF induced by BLM, the lower the autophagy activity.

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