2,4-Dichlorophenoxyacetic acid (2,4-D), a member of the phenoxy family of herbicides is commonly used in agriculture for controlling broadleaf weeds but its uncontrolled and incoherent use has been linked to incidences of lung toxicity. The present study aimed to understand the molecular mechanisms behind the 2,4-D alone or in combination with endotoxin (lipopolysaccharide [LPS]) induced pulmonary toxicity. Blood and lung samples were collected from Swiss albino mice (n = 48) following chronic exposure to high (37 mg/kg; 1/10th of LD₅₀) and low (18.5 mg/kg; 1/20th of LD₅₀) doses of 2,4-D alone or in combination with endotoxin (80 µg/animal). Transcriptome analysis revealed Wnt Canonical signaling as one of the top dysregulated pathways in mice lung following exposure to 2,4-D with and without endotoxin (LPS) co-exposure. Global view of differentially expressed genes showed increased messenger RNA expression of Axin2 by 0.26, 2.58, 3.14, 2.59, and 2.97 folds following exposure to LPS, high dose alone or in combination with LPS and low dose alone or in combination with LPS, respectively. The microarray data were validated using quantitative polymerase chain reaction and immunohistochemistry. Furthermore, the plasma concentration of Axin2 was elevated in the high dose group as revealed by Sandwich ELISA. The data taken together suggest a role of Axin2 to activate the Canonical Wnt signaling pathway in 2,4-D and or endotoxin-induced lung damage in mice.

中文翻译：

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暴露于含或不含内毒素的除草剂 2,4-D 的小鼠肺 Axin2 水平升高

2,4-二氯苯氧乙酸 (2,4-D) 是苯氧基类除草剂的成员，常用于农业控制阔叶杂草，但其不受控制和不连贯的使用与肺毒性的发生率有关。本研究旨在了解 2,4-D 单独或与内毒素（脂多糖 [LPS]）联合诱导肺毒性背后的分子机制。_{在长期暴露于高浓度（37 mg/kg；LD 50} 的 1/10 ）和低浓度（18.5 mg/kg；LD ₅₀的 1/20 ）后，从瑞士白化小鼠 ( n = 48)收集血液和肺样本) 2,4-D 单独剂量或与内毒素联合剂量（80 µg/动物）。转录组分析显示 Wnt Canonical 信号传导是小鼠肺在暴露于 2,4-D （有和没有内毒素 (LPS) 共同暴露后）中最严重的失调通路之一。差异表达基因的全局视图显示，在暴露于 LPS、单独高剂量或与 LPS 组合和单独低剂量或与 LPS 组合后，Axin2 的信使 RNA 表达分别增加了 0.26、2.58、3.14、2.59 和 2.97 倍。使用定量聚合酶链反应和免疫组织化学验证微阵列数据。此外，夹心 ELISA 显示，高剂量组中 Axin2 的血浆浓度升高。综合数据表明 Axin2 在 2 中激活典型 Wnt 信号通路的作用，