WISP1 对百草枯诱导的 EMT 的影响。
Effect of WISP1 on paraquat-induced EMT.
机构信息
Department of Emergency, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong 518172, PR China.
Department of Out-patient, Linyi People's Hospital, Linyi 276000, Shandong, China.
出版信息
Toxicol In Vitro. 2023 Dec;93:105693. doi: 10.1016/j.tiv.2023.105693. Epub 2023 Sep 7.
BACKGROUND
Paraquat (PQ) can induce pulmonary fibrosis (PF) by modulating epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, but the molecular mechanism is unknown. In this paper, the role of Wnt-inducible signaling protein-1 (WISP1) in PQ-induced EMT was inspected.
METHODS
The morphology, apoptosis, and mortality of A549 cells were observed through a microscope. The mRNA and protein levels of WISP1, E-cadherin, and Vimentin were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot.
RESULTS
With the increase of PQ concentration, the morphology of A549 cells was apparently changed, cell apoptosis and mortality were enhanced. Besides, the E-cadherin abundance was reduced (p < 0.01), however, WISP1 and Vimentin contents were boosted after PQ treatment (p < 0.01). With the increase of PQ treatment time, the epithelial index of cells first increased and then decreased. The expression of WISP1 gene increased significantly with the increase of PQ treatment time (p < 0.01). Silence of WISP1 abolished the effect of PQ treatment on E-cadherin and Vimentin levels (p < 0.01). Downregulation of WISP1 curbed morphology change and PQ-induced EMT in A549 cells.
CONCLUSION
Knockdown of WISP1 inhibited PQ-induced EMT in A549 cells. This conclusion might provide a new therapeutic target for PQ poisoning treatment.
背景
百草枯（PQ）可通过调节肺泡上皮细胞的上皮-间充质转化（EMT）诱导肺纤维化（PF），但其分子机制尚不清楚。本文研究了 Wnt 诱导信号蛋白-1（WISP1）在 PQ 诱导 EMT 中的作用。
方法
通过显微镜观察 A549 细胞的形态、凋亡和死亡率。通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹法验证 WISP1、E-钙黏蛋白和波形蛋白的 mRNA 和蛋白水平。
结果
随着 PQ 浓度的增加，A549 细胞的形态明显改变，细胞凋亡和死亡率增加。此外，E-钙黏蛋白丰度降低（p<0.01），而 WISP1 和波形蛋白含量增加（p<0.01）。随着 PQ 处理时间的增加，细胞的上皮指数先增加后减少。WISP1 基因的表达随着 PQ 处理时间的增加而显著增加（p<0.01）。沉默 WISP1 消除了 PQ 处理对 E-钙黏蛋白和波形蛋白水平的影响（p<0.01）。下调 WISP1 抑制了 A549 细胞的形态变化和 PQ 诱导的 EMT。
结论
敲低 WISP1 抑制了 A549 细胞中 PQ 诱导的 EMT。这一结论可能为 PQ 中毒治疗提供新的治疗靶点。
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