Mechanistic Insights Into the Role of Selenoprotein M in Nickel-Induced Lung Fibrosis.

Long-term exposure to high concentrations of nickel (Ni) compounds could cause damage to lung tissue and increase the risk of lung and respiratory cancers. Selenoprotein M (SELENOM) plays a crucial role in antioxidant and anti-inflammatory activities. However, the relationship between SELENOM and the mechanism of Ni-induced pulmonary fibrosis in mice remains unknown. Our study explored the regulated mechanism of SELENOM in Ni-induced pulmonary fibrosis. Wild-type and SELENOM knockout C57BL/6N male mice were randomly divided into Wild-control and Wild-Ni groups, which were administered distilled water and NiCl₂ (10 mg/kg) by gavage for 21 days. Lung tissues were then collected for histological analysis using hematoxylin-eosin (H&E) and Masson staining, as well as for electron microscopic examination. Firstly, light microscopy revealed inflammatory cell infiltration, alveolar collapse, and alveolar wall thickening in the lung tissue of SELENOM knockout mice. Electron microscopy of lung tissue showed a large accumulation of fibroblasts, proliferation of collagen fibers, and dense collagen deposition, indicating that SELENOM knockout increased lung injury in Ni treatment. Secondly, SELENOM knockout increased malondialdehyde (MDA) levels while decreasing superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) activities. Furthermore, Ni exposure and SELENOM knockout significantly upregulated protein and mRNA levels of epithelial-mesenchymal transition (EMT) markers α-SMA, COL-I, TGF-β1/Smad, and JAK2/STAT3 signaling pathway in the lung. These findings suggest that SELENOM knockout promotes EMT and exacerbates pulmonary fibrosis and inflammation through activation of the TGF-β1/Smad and JAK2/STAT3 signaling pathways. In summary, our study highlights the critical role of SELENOM in mitigating Ni-induced pulmonary fibrosis and provides insights into potential therapeutic targets for Ni-induced lung diseases.