Idiopathic pulmonary fibrosis (IPF) is an idiopathic interstitial lung disease. At present, the pathogenesis of IPF has not been fully elucidated, which has affected the development of effective treatment methods. Here, we explored the function and potential mechanism of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS1) in IPF.Transforming growth factor-β (TGF-β) and bleomycin (BLM) were used to induce IPF in cells and animal models. Real Time quantitative Polymerase Chain Reaction (RT-qPCR) showed the expression of CDKN2B-AS1, miR-199a-5p and Sestrin-2 (SESN2) in cells and tissues. The double luciferase reporter gene assay confirmed the targeting relationship among CDKN2B-AS1, miR-199a-5p, and SESN2. Related protein levels were detected by Western blot combined with Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry to analyze cell proliferation, migration, and apoptosis. The pathological characteristics of mouse lung tissue were determined by Hematoxylin-eosin (HE) and Masson staining. We found that the expression of CDKN2B-AS1 was decreased in TGF-β-treated cells and BLM-treated mice. Overexpression of CDKN2B-AS1 inhibited cell proliferation and migration, promoted apoptosis, decreased the expression of fibrosis-related proteins and promoted autophagy. In addition, overexpression of CDKN2B-AS1 alleviated pulmonary fibrosis in BLM-treated mice. Mechanistically, CDKN2B-AS1 acts as a miR-199a-5p sponge to regulate SESN2 expression. Our results indicate the importance of the CDKN2B-AS1/miR-199a-5p/SESN2 axis.
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.
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