Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Environ Toxicol Pharmacol. 2024 Jan;105:104329. doi: 10.1016/j.etap.2023.104329. Epub 2023 Nov 28.
Exposure to particulate matter ≤ 2.5 µm (PM) is a risk factor for many lung diseases. Although the toxicologic effects of PM on airway epithelium are well-described, the effects of PM on fibroblasts in the lung are less studied. Here, we sought to examine the effects of PM on the differentiation of fibroblasts into myofibroblasts. Although a single treatment of fibroblasts did not result in a change in collagen or the myofibroblast marker α-SMA, exposing fibroblasts to sequential treatments with PM at low concentrations caused a robust increase in these proteins. Treatment of fibroblasts with IMD0354, an inhibitor to nuclear factor κB, but not with an antagonist to aryl hydrocarbon receptor, abolished the ability of PM to induce myofibroblast differentiation. These data demonstrate that potential impact of PM to fibroblast activation and fibrosis and support the importance of utilizing low concentrations and varying exposure protocols to toxicologic studies.
暴露于≤2.5μm 的颗粒物（PM）是许多肺部疾病的危险因素。尽管 PM 对气道上皮的毒理学效应已有详细描述，但 PM 对肺部成纤维细胞的影响研究较少。在这里，我们试图研究 PM 对成纤维细胞分化为肌成纤维细胞的影响。尽管成纤维细胞单次处理不会导致胶原蛋白或肌成纤维细胞标志物α-SMA 发生变化，但用低浓度的 PM 进行连续处理会导致这些蛋白质大量增加。用 IMD0354（核因子 κB 的抑制剂）处理成纤维细胞，但不用芳基烃受体拮抗剂处理成纤维细胞，可消除 PM 诱导肌成纤维细胞分化的能力。这些数据表明 PM 对成纤维细胞激活和纤维化的潜在影响，并支持在毒理学研究中使用低浓度和不同暴露方案的重要性。
