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Protective mechanism of retinoic acid on primary cultured alveolar type Ⅱ epithelial cells under hyperoxia |
PAN Qiqi* MA Jinshuai* LIU Xiuxiang LYU Meng |
Department of Neonatology, Affiliated of Binzhou Medical University, Shandong Province, Binzhou 256600,China |
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Abstract Objective To investigate protective mechanism of retinoic acid on primary cultured alveolar type Ⅱ epithelial cells under hyperoxia. Methods Alveolar type Ⅱ epithelial cells were isolated and purified from fetal rat lung tissue at 19 days of gestation. When the cells grew to the fused state (80% bottle bottom), the cells were divided into air group, hyperoxia group and hyperoxygenation + RA group. The apoptosis of AECⅡ was detected by flow cytometry, the β-catenin protein expression of Wnt signal pathway was detected by Western blot, and the β-catenin gene expression was detected by PCR. Results Compared with the air group and the hyperoxygenation + RA group, the AECⅡ number of AnnexinV (+) PI (-) and AnnexinV (+) PI (+) markers in the hyperoxia group was significantly higher at 24 h of exposure (P < 0.01), and the cell number was significantly reduced after RA addition. Compared with the air group, the expression of β-catenin protein of the hyperoxia group was significantly decreased, the difference was statistically significant (P < 0.01), while compared with the high oxygen group, the expression of β-catenin protein of the hyperoxygenation + RA group was upregulated significantly (P < 0.01). Conclusion Hyperaerobic environment can lead to massive apoptosis and necrosis of AECⅡ, and RA can reduce apoptosis of this cell by up-regulating the expression of β-catenin protein, thus playing a protective role in hyperoxic lung injury.
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[1] 马金帅,刘秀香,杨建英,等.Wnt7b/β-catenin信号通路分子在肺泡Ⅱ型上皮细胞转分化过程中的变化[J].细胞与分子免疫学杂志,2015,31(10):1332-1335,1341.
[2] Rozak AS,Lam AP,Russell S,et al. Beta-catenin/T-cell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells [J]. J Biol Chem,2010,285(5):3157-3167.
[3] Fiaturi N,Russo JW,Nielsen HC. CCN5 in alveolar epithelial proliferation and differentiation during neonatal lung oxygen injury [J]. Cell Commun Signal,2018,12(1):217-229.DOI:10.1007/s12079-017-0443-1
[4] 董欣鑫.神经肽P物质对95%氧致AECⅡ细胞损伤的氧化抗氧化作用及Wnt信号通路的相关研究[D].重庆:重庆医科大学,2013.
[5] Xu S,Xue X,You K. Caveolin-1 regulates the expression of tight junction proteins during hyperoxia-induced pulmonary epithelial barrier breakdown [J]. Respir Res,2016, 17(1):50.
[6] Zhang QY,Fu JH. Expression and function of aquaporin-1 in hyperoxia-exposed alveolar epithelial type Ⅱ cells [J]. Exp Ther Med,2014,8(2):493-498.
[7] Chen HJ. Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice [J]. PLoS One,2015,10(10):e0140343.
[8] Stenger MR, Rose MJ, Joshi MS,et al. Inhaled nitric oxide prevents 3-nitrotyrosine formation in the lungs of neonatal mice exposed to>95% oxygen [J]. Lung,2010,188(3):217-227.
[9] Paul S,Dey A. Wnt signaling and cancer development:therapeutic im plication [J]. Neo Plasma,2008,55(3):165-176.
[10] Wang S,Dang H,Xu F,et al. The Wnt7b/β-catenin signaling pathway is involved in the protective action of calcitonin gene-related peptide on hyperoxia-induced lung injury in premature rats [J]. Cell Mol Biol Lett,2018, 23:4.
[11] Tebar M,Destrée O,de Vree WJ. Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung [J]. Mech Dev,2001,109(2):437-440.
[12] Huelsken J,Vogel R,Brinkmann V,et al. Requirement for beta-catenin in anterior-posterior axis formation in mice [J]. Cell Biol,2000,148(3):567-578.
[13] Rajagopal J,Carroll TJ,Guseh JS,et al. Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme [J]. Development(Cambridge,England),2008,135(9):1625-1634.
[14] Pongracz JE,Stoekley RA. Wnt signaling in lung development and diseases [J]. Respir Res,2006,7:15.
[15] 李文斌,常立文,容志惠,等.维甲酸通过MAPKs信号通路减轻早产大鼠AECⅡ高氧性损伤[J].中国病理生理杂志,2008,24(1):1-6.
[16] 高瑞伟.RA及IL-24对胎鼠肺泡Ⅱ型上皮细胞增殖及转分化的影响[D].滨州:医学院滨州医学院,2015.
[17] 赵鹏.高氧暴露对新生大鼠肺组织中VEGF、β-catenin、DKK-1蛋白表达的影响[D].苏州:苏州大学,2016.
[18] 潘丽.β-catenin在高氧致新生鼠BPD中的作用及其机制的研究[D].沈阳:中国医科大学,2009.
[19] De Langhe SP.Wnt signaling in lung organogenesis [J]. Organogenesis,2008,4(2):100-108.
[20] Cohen JC,Larson JE,Killeen E,et al. CFTR and Wnt/beta-catenin signaling in lung development [J]. BMC Dev Biol,2008,8:70.DOI:10.1186/1471-213X-8-70 |
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