Downregulation of miR-410-3p via the METRNL-mediated AMPK/SIRT1/NF-κB signaling axis inhibits oxidative stress and inflammation in idiopathic pulmonary fibrosis.

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Tác giả: Zhaoxing Dong, Tongjie Gu, Qiong Wang, Chunli Wu, Ying Zhou, Xiaoxiao Zhu

Ngôn ngữ: eng

Ký hiệu phân loại: 553.3 Iron

Thông tin xuất bản: England : Cellular signalling , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 511077

Idiopathic pulmonary fibrosis (IPF), a fatal pulmonary condition, is marked by fibrosis and is devoid of efficacious treatments. The aim of our research was to explore the influence of miR-410-3p on the advancement of IPF. For creating a model of lung fibrosis, tracheal injections of 5 mg/kg bleomycin (BLM) were administered to mice, and added 10 ng/mL of TGF-β1 into MRC-5 cell medium. The evaluation of gene and protein expression was conducted using RT-qPCR and western blotting techniques. The assessment of fibrosis in MRC-5 cells and mouse pulmonary tissue involved the use of CCK-8, ELISA, flow cytometry, and HE staining methods. The results of our study revealed a rise in miR-410-3p levels in both TGF-β1-stimulated MRC-5 cells and BLM-exposed mouse pulmonary tissue. Inhibiting miR-410-3p decreased cell viability, lessened oxidative stress (MDA, ROS), decreased levels of inflammatory cytokines (TNF-α, IL-1β, IL-6), curtailed fibrosis-associated proteins (α-SMA, Collagen I, Collagen III, FN1), and amplified the expression of SOD and E-cadherin. The treatment effectively reduced cell fibrosis and improved lung tissue health, thus hindering the advancement of IPF. Mechanically, knocking down miR-410-3p activates AMPK/SIRT1 molecular axis to inhibit NF-κB signaling by up-regulating METRNL expression, thereby inhibiting oxidative stress and inflammation levels, and ultimately improving IPF. In summary, our research indicates that focusing on miR-410-3p might be an effective approach in IPF treatment.
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