PPP2R3A通过调控p53的表达促进矽肺肺纤维化

史晓妮; 杨少奇; 成于思; 巢杰

doi:10.11665/j.issn.1000-5048.20220412

PPP2R3A通过调控p53的表达促进矽肺肺纤维化

史晓妮^1,2,
杨少奇^1,2,
成于思²,
巢杰^1,2

1.
东南大学公共卫生学院环境医学工程教育部重点实验室，南京 210009
2.
东南大学医学院生理学系，南京 210009

基金项目: 国家自然科学基金资助项目（No.81972987）

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出版历程
- 收稿日期: 2022-05-09
- 修回日期: 2022-06-20
- 刊出日期: 2022-08-24

PPP2R3A promotes silicosis by regulating the expression of p53

1.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009
2.
Department of Physiology, School of Medicine, Southeast University, Nanjing 210009, China

Funds: This study was supported by the National Naturac Science Foundation of China (No.81972987)

摘要

摘要: 矽肺是世界范围内较严重的职业病之一，其发病机制尚未完全阐释清楚。蛋白磷酸酶2A（PP2A）具有调节肿瘤信号通路、细胞发育进程及细胞周期的功能，PP2A的调节亚基B与核心酶结合，导致PP2A全酶复合物的组织表达特异性和底物特异性。蛋白磷酸酶2A调节亚基B″α（PPP2R3A）是PP2A调节亚基B″中的一个亚基，是细胞增殖的调节因子，但目前的研究尚不清楚PPP2R3A在肺纤维化中所发挥的作用。本研究采用气管滴注二氧化硅（SiO₂，250 mg/kg）构建肺纤维化模型；采用5 ng/mL TGF-β1刺激人肺成纤维细胞（HPF-a）构建纤维化相关的细胞模型；qRT-PCR实验检测Ppp2r3a转录水平；免疫荧光和蛋白免疫印迹实验检测蛋白水平；采用CCK-8实验检测细胞活力；划痕实验检测细胞迁移能力。实验结果表明，SiO₂模型组小鼠出现矽结节且胶原沉积明显，PPP2R3A在肺脏成纤维细胞中表达上升，可以影响细胞的活力和迁移能力，且可能通过调控p53信号通路的表达促进肺纤维化的进程。本研究为肺纤维化的防治提供了新的思路。
- PPP2R3A /
- 矽肺 /
- 肺纤维化 /
- 二氧化硅 /
- p53信号通路
Abstract: Silicosis, one of the most serious occupational diseases in the world, is a complex pathological process with multi-cell involvement and multi-factor regulation, and its pathogenesis has not been fully elucidated.Protein phosphatase 2A (PP2A) regulates tumor signaling pathways, cell development and cell cycle.The regulatory subunit B of PP2A binds to the core enzyme, resulting in tissue expression specificity and substrate specificity of the PP2A holoenzyme complex.Protein phosphatase 2A regulatory subunit B"α (PPP2R3A) is a subunit of PP2A regulatory subunit B", which is a regulator of cell proliferation.However, the role of PPP2R3A in pulmonary fibrosis is still unclear.In this study, the pulmonary fibrosis model was established by endotracheal infusion of silica (SiO₂, 250 mg/kg).Human pulmonary fibroblast-adult cells (HFP-a) were stimulated with 5 ng/mL TGF-β1 to construct fibro-related cell models.The transcription level of Ppp2r3a was detected by qRT-PCR assay.Immunofluorescence and Western blot experiments were performed to detect protein levels.Cell viability was detected by CCK-8 assay.The cell migration ability was detected by scratch test.Experimental results showed that silica nodules and collagen deposition were obvious in the SiO₂ group, and the expression of PPP2R3A in lung fibroblasts increased, which could affect cell viability and migration ability, and may promote the progression of pulmonary fibrosis by regulating the expression of p53 signaling pathways.This study provides a new idea for the prevention and treatment of pulmonary fibrosis.
- PPP2R3A /
- silicosis /
- pulmonary fibrosis /
- silica /
- p53 signaling pathways

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