Role and Mechanism of Keap1/Nrf2 Signaling Pathway in the Regulation of Autophagy in Alleviating Pulmonary Fibrosis

Comput Intell Neurosci. 2022 Jul 18:2022:3564871. doi: 10.1155/2022/3564871. eCollection 2022.

Abstract

A variety of internal and external lung diseases may eventually lead to pulmonary fibrosis, and insufficient autophagy is closely related to pulmonary fibrosis. This research is aimed to explore the mechanism of autophagy to alleviate pulmonary fibrosis. Then, a mouse model of pulmonary fibrosis induced by boromycin and histopathological lesions of the lungs of mice were observed by HE staining, which Masson staining assessed the degree of fibrosis in the lung tissue by detecting the expression of hydroxyproline in the tissue. RT-qPCR and western blotting were used to detect the levels of autophagy and Keap1/Nrf2 signaling pathway-related proteins. It was proved that autophagy-related proteins MAP1LC3(LC3) and Beclin 1 were decreased in mice with pulmonary fibrosis, while the expression of p62 was increased. Mice with pulmonary fibrosis worsened after injection of a 3-MA autophagy inhibitor, while injection of autophagy activation of rapamycin agent promoted Nrf2 nuclear mobilization. In a word, autophagy relieves pulmonary fibrosis through the activation of the Keap1/Nrf2 signaling pathway.

MeSH terms

  • Animals
  • Autophagy
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Mice
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Pulmonary Fibrosis*
  • Signal Transduction

Substances

  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2