The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, PR China.
The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, PR China.
Toxicol Appl Pharmacol. 2021 Dec 1;432:115757. doi: 10.1016/j.taap.2021.115757. Epub 2021 Oct 19.
An increasing number of studies have shown that arsenic exposure increases the risk of lung cancer as well as a variety of non-malignant respiratory diseases, including bronchitis and tracheobronchitis. HMGB1 is widely expressed in a variety of tissues and cells and is involved in the pathological processes of many lung diseases through binding to the corresponding receptors and activating the downstream signaling pathways. However, the exact role of HMGB1/RAGE in arsenic-induced lung injury remains unknown. The aim of this study was to investigate whether HMGB1/RAGE and its activated downstream pathways are involved in the process of arsenic exposure-induced lung injury in rats. In this study, an animal model of oral exposure to arsenic was induced using 2.5, 5 and 10 mg/kg NaAsO. The results showed that capillary permeability (LDH, TP, ACP, and AKP) was increased in the arsenic exposure groups, resulting in cell damage; this was accompanied by acute inflammation marked by significant neutrophil infiltration. Meanwhile, obvious histopathological damage, including thickening of the lung epithelium, increased infiltration of inflammatory cells, rupture of the alveolar wall, swelling of the mitochondria, and chromatin agglutination was observed by H&E staining and transmission electron microscopy. Furthermore, the results confirmed that the expressions of HMGB1 and RAGE in lung tissue were enhanced, and protein expression of PI3K, p-AKT, IL-1β, IL-18, and MMP-9 was increased in lung homogenates from the arsenic-exposed groups compared to the control group. Finally, Masson's staining results revealed arsenic-induced fibrosis and collagen deposition. Moreover, a significant increase in key fibrosis factors, including TGF-β1, p-SMAD2, p-SMAD3, and SMAD4 was observed in the lung homogenates in arsenic-exposed groups. In conclusion, the current study demonstrates that sub-chronic arsenic exposure triggers the inflammatory response and collagen fiber deposition in rat lung tissue. The potential mechanism may be closely related to activation of the pro-inflammatory-related HMGB1/RAGE pathway and initiation of the PI3K/AKT and TGF-β1/SMAD pathways.
越来越多的研究表明，砷暴露会增加肺癌以及各种非恶性呼吸道疾病的风险，包括支气管炎和气管支气管炎。HMGB1 广泛表达于多种组织和细胞中，通过与相应的受体结合并激活下游信号通路，参与多种肺部疾病的病理过程。然而，HMGB1/RAGE 在砷诱导的肺损伤中的确切作用尚不清楚。本研究旨在探讨 HMGB1/RAGE 及其激活的下游通路是否参与了大鼠砷暴露诱导的肺损伤过程。在这项研究中，使用 2.5、5 和 10mg/kg NaAsO2 诱导口服暴露于砷的动物模型。结果表明，砷暴露组的毛细血管通透性（LDH、TP、ACP 和 AKP）增加，导致细胞损伤；同时伴有明显的中性粒细胞浸润的急性炎症。此外，通过 H&E 染色和透射电镜观察到明显的组织病理学损伤，包括肺上皮增厚、炎症细胞浸润增加、肺泡壁破裂、线粒体肿胀和染色质凝集。进一步证实，砷暴露组肺组织中 HMGB1 和 RAGE 的表达增强，肺匀浆中 PI3K、p-AKT、IL-1β、IL-18 和 MMP-9 的蛋白表达增加。最后，Masson 染色结果显示砷诱导的纤维化和胶原沉积。此外，在砷暴露组的肺匀浆中观察到关键纤维化因子 TGF-β1、p-SMAD2、p-SMAD3 和 SMAD4 的表达显著增加。综上所述，本研究表明，亚慢性砷暴露会引发大鼠肺组织的炎症反应和胶原纤维沉积。其潜在机制可能与促炎相关的 HMGB1/RAGE 通路的激活以及 PI3K/AKT 和 TGF-β1/SMAD 通路的启动密切相关。
