Guan Haoyue, Sun Yue, Qiao Senqiu, Li Di, Cai Jingzeng, Zhang Ziwei
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, P. R. China.
College of Animal Science and Veterinary Medicine, Sichuan Agricultural University, Chengdu, 625014, P. R. China.
Biol Trace Elem Res. 2025 Apr 28. doi: 10.1007/s12011-025-04636-8.
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 NiCl (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.
长期暴露于高浓度镍（Ni）化合物会导致肺组织损伤，并增加患肺癌和呼吸道癌症的风险。硒蛋白M（SELENOM）在抗氧化和抗炎活动中起关键作用。然而，SELENOM与小鼠镍诱导的肺纤维化机制之间的关系尚不清楚。我们的研究探讨了SELENOM在镍诱导的肺纤维化中的调控机制。将野生型和SELENOM基因敲除的C57BL/6N雄性小鼠随机分为野生对照组和野生镍组，分别通过灌胃给予蒸馏水和NiCl（10 mg/kg），持续21天。然后收集肺组织，用苏木精-伊红（H&E）和Masson染色进行组织学分析，并进行电子显微镜检查。首先，光学显微镜显示SELENOM基因敲除小鼠的肺组织中有炎性细胞浸润、肺泡塌陷和肺泡壁增厚。肺组织的电子显微镜检查显示成纤维细胞大量积聚、胶原纤维增生和致密的胶原沉积，表明SELENOM基因敲除增加了镍处理后的肺损伤。其次，SELENOM基因敲除增加了丙二醛（MDA）水平，同时降低了超氧化物歧化酶（SOD）、总抗氧化能力（T-AOC）和谷胱甘肽过氧化物酶（GSH-Px）的活性。此外，镍暴露和SELENOM基因敲除显著上调了肺中上皮-间质转化（EMT）标志物α-SMA、COL-I、TGF-β1/Smad和JAK2/STAT3信号通路的蛋白质和mRNA水平。这些发现表明，SELENOM基因敲除通过激活TGF-β1/Smad和JAK2/STAT3信号通路促进EMT并加剧肺纤维化和炎症。总之，我们的研究突出了SELENOM在减轻镍诱导的肺纤维化中的关键作用，并为镍诱导的肺部疾病提供了潜在治疗靶点的见解。
