Caveolin-1 negatively regulates inflammation and fibrosis in silicosis.
Caveolin-1 negatively regulates inflammation and fibrosis in silicosis.
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DOI：
10.1111/jcmm.17045
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发表时间：
2022-01
影响因子：
5.3
通讯作者：
Meng J
中科院分区：
文献类型：
--
作者：
He R;Yuan X;Lv X;Liu Q;Tao L;Meng J
吸入结晶二氧化硅会导致硅肺病，这是最常见和最严重的职业病，其特征是进行性肺部炎症和纤维化。最近的研究揭示了 Caveolin-1 (Cav-1) 在肺中的抗炎和抗纤维化作用，但尚未研究其在矽肺中的作用。因此，本研究评估了 Cav-1 对矽肺的调节作用。研究发现，矽肺患者和矽肺小鼠肺部的 Cav-1 水平显着降低。在 C57BL/6（野生型）和 Cav-1 缺陷型（Cav-1 −/−）小鼠中建立矽肺模型，Cav-1 −/− 小鼠表现出更宽的肺泡间隔、增加的胶原沉积和更多的矽肺结节。利用小鼠腹膜来源的巨噬细胞来探索 Cav-1 在二氧化硅诱导的炎症中的作用，该炎症在硅肺发病机制中发挥着核心作用。 Cav-1 在体外和体内抑制二氧化硅诱导的炎症细胞浸润和炎症因子的分泌，部分是通过下调 NF-κB 通路来实现的。此外，观察了硅质小鼠的二氧化硅摄取和4-羟基壬烯醛的表达，发现Cav-1的缺失引发了过量的二氧化硅沉积，引起更强的氧化应激反应。这些发现证明了 Cav-1 对二氧化硅引起的肺损伤的保护作用，表明其在矽肺中的潜在治疗价值。
Inhalation of crystalline silica causes silicosis, the most common and serious occupational disease, which is characterized by progressive lung inflammation and fibrosis. Recent studies revealed the anti‐inflammatory and anti‐fibrosis role of Caveolin‐1 (Cav‐1) in lung, but this role in silicosis has not been investigated. Thus, this study evaluated Cav‐1 regulatory effects in silicosis. It was found that Cav‐1 levels were significantly reduced in the lung from silicosis patients and silicotic mice. The silicosis models were established in C57BL/6 (wild‐type) and Cav‐1 deficiency (Cav‐1 −/−) mice, and Cav‐1 −/− mice displayed wider alveolar septa, increased collagen deposition and more silicotic nodules. The mice peritoneal‐derived macrophages were used to explore the role of Cav‐1 in silica‐induced inflammation, which plays a central role in mechanism of silicosis. Cav‐1 inhibited silica‐induced infiltration of inflammatory cells and secretion of inflammatory factors in vitro and in vivo, partly by downregulating NF‐κB pathway. Additionally, silica uptake and expression of 4‐hydroxynonenal in silicotic mice were observed, and it was found that Cav‐1 absence triggered excessive silica deposition, causing a stronger oxidative stress response. These findings demonstrate the protective effects of Cav‐1 in silica‐induced lung injury, suggesting its potential therapeutic value in silicosis.
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