Research progress on mechanism of epithelial mesenchymal transition induced by chrysotile exposure
-
摘要:
温石棉是生活中广泛应用的矿物材料，其致纤维化、致癌性是公众关注较多的公共卫生问题。目前，已有50多个国家全面禁止进口和使用温石棉，但中国仍是世界上最大的温石棉消费国和第二大生产国，职业暴露人群庞大。调查显示温石棉矿工患肺纤维化、肺癌和间皮瘤的概率明显高于其他职业工作者。但温石棉诱发癌症的潜伏期一般长达数十年，难以及时发现和治疗，因此温石棉暴露所致的癌症死亡人数较多，是职业性癌症死亡的主要原因。上皮间质转化是组织、器官发生慢性炎症、纤维化、癌变及癌转移等生物学过程的关键步骤，在温石棉暴露所致肺纤维化、肺癌及其他疾病中发挥着重要作用。本文主要从炎症因子的表达水平变化、丝裂原活化蛋白激酶通路及氧化应激等其他生物学途径对温石棉诱导上皮间质转化的机制研究现状进行概述，并提出进一步研究温石棉诱导上皮间质转化可能的研究方向，为深入研究温石棉暴露对肺纤维化、肺癌等疾病的发生发展奠定基础，提供可靠的依据与参考。
Abstract:As a mineral material widely used in life, chrysotile is a public health concern for its fibrogenicity and carcinogenicity. Currently, more than 50 countries have completely banned the import and use of chrysotile, but China is still the world's largest consumer and second largest producer of chrysotile, with a large occupationally exposed population. Investigations have shown that chrysotile miners are significantly more likely to develop pulmonary fibrosis, lung cancer, and mesothelioma than workers in other occupations. Chrysotile-induced cancers generally have a decades-long latency period and are difficult to diagnose and treat in a timely manner. Therefore, the cancer fatality due to chrysotile exposure is significant and is a leading contributor to occupational cancer death. Epithelial mesenchymal transition is a key step in the biological processes of chronic inflammation, fibrosis, carcinogenesis, and cancer metastasis in tissues and organs, also plays an important role in pulmonary fibrosis, lung cancer, and other diseases due to chrysotile exposure. This paper summarized the mechanisms of chrysotile inducing epithelial interstitial transition from dynamics of inflammatory factors, mitogen-activated protein kinase pathways, oxidative stress, and other biological pathways, and proposed possible research directions for further study on chrysotile-induced epithelial mesenchymal transition, aiming to provide a reliable basis and reference for in-depth research on pulmonary fibrosis, lung cancer, and other diseases due to chrysotile exposure.
-
温石棉是自然界中储量丰富的矿物纤维材料，具有耐腐蚀、耐高温、绝缘性好等特点，广泛应用于纺织、建材、化工、机械和国防等领域。中国的温石棉矿产丰富，全国超百万人被职业暴露，且近年来温石棉暴露所致疾病的发病率呈上升趋势[1]。温石棉通过呼吸过程进入人体，穿透呼吸道防御屏障，沉积于肺部，对肺和胸膜的损害较大，可导致肺纤维化、石棉肺、肺癌和胸膜间皮瘤等疾病，且长期接触温石棉会使肺癌风险增加6倍，肺纤维化风险增加3倍[2]。上皮间质转化（epithelial mesenchymal transition, EMT）是上皮细胞失去上皮特征获得间充质细胞迁移性的过程，具有促进肺纤维化，增强肺肿瘤细胞迁移和侵袭的特征[3]。研究显示，温石棉长期暴露诱导EMT主要与炎症因子水平变化和丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）/细胞外调节蛋白激酶（extracellular regulated protein kinase, ERK）通路的激活等有关[4-6]。因此，为深入研究温石棉如何促进肺纤维化和肺癌等疾病的发生，本文总结了温石棉暴露诱导EMT的机制研究现状。
1. 炎症因子水平变化
在炎症微环境中，多种炎症因子在参与炎症的同时，也参与对EMT的调控。炎症因子是细胞经刺激而合成、分泌的小分子可溶性蛋白质，通过不同的通路调节机体的炎症反应。研究表明，温石棉暴露可改变转化生长因子-β（transforming growth factor-β, TGF-β）、高迁移率族蛋白B1（high mobility group box1, HMGB1）、肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α)和白介素（interleukin, IL）-1β等炎症因子的表达水平[7-8]。因此，研究炎症因子的表达水平有助于探讨温石棉诱导EMT的机制。
1.1 TGF-β
TGF-β作为多功能蛋白，其关键作用是调节炎症相关反应，同时也可通过多种正、负反馈调节机制调控细胞生长、分化以及细胞外基质的产生[9]。TGF-β被认为是诱导EMT的主要诱导剂之一，主要经SMAD（small mothers against decapentaplegic）蛋白途径和SMAD非依赖途径介导。SMAD途径中，TGF-β信号通过与I型和II型TGF-β受体（TGF-β receptor, TGF-βR），即TGF-βRI、TGF-βRII结合，使磷酸化的SMAD2/3与SMAD4结合形成复合物发挥正反馈作用介导EMT[10]；SMAD6和SMAD7通过负反馈调节抑制SMAD受体的激活，阻断信号的传导[11]。SMAD非依赖途径通过活化的蛋白激酶B（protein kinases B, Akt）或磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase, PI3K）等进行转录调控介导EMT[12]。
研究表明，温石棉暴露可通过诱导肺上皮细胞过度表达TGF-β促进EMT，参与肺纤维化等病理过程[13]。Gulino等[14]发现长期暴露于温石棉的人肺上皮细胞系BEAS-2B细胞分泌TGF-β，并通过SMAD非依赖性途径Akt / 糖原合成酶激酶-3β（glycogen synthase kinase-3β, GSK-3β） / Snail家族转录抑制因子1（Snail-1）诱导发生EMT。Turini等[4]通过比较暴露于温石棉或TGF-β的MeT-5A细胞中SMAD2及EMT标志物的表达水平，发现温石棉可通过TGF-β介导的SMAD途径诱导EMT。可见，TGF-β介导的SMAD途径和SMAD非依赖途径为探讨温石棉诱导EMT的机制提供了可靠依据。
1.2 HMGB1
HMGB1是一种核蛋白，不仅能参与细胞分化过程，还可作为促炎因子诱导炎症因子的产生。大量研究表明，HMGB1作为上游因子调控TGF-β1、IL-6、TNF-α等炎症因子的表达与EMT的发生密切相关[15-16]。HMGB1既能促进TGF-β1的表达，还可通过抑制SMAD2/3[17]和SMAD1[18]通路的信号传导来逆转TGF-β1诱导的EMT。Hao等[19]证实，抑制HMGB1的表达会导致IL-6、IL-8和TNF-α等炎症因子表达水平降低，从而抑制EMT的发生。此外，HMGB1也可在部分非编码RNA的调控下介导EMT，如长链非编码RNA（long non-coding RNA, lncRNA）牛磺酸上调基因1 (taurine upregulated gene 1, TUG1）海绵吸附于miR-181b上调HMGB1的表达，从而促进鼠气道组织EMT[20]。以上说明HMGB1作为重要介质可通过多种调控途径介导EMT。
现有学者提出HMGB1可作为温石棉相关疾病的潜在生物标志物[8]。温石棉暴露使HMGB1的表达水平发生改变，且HMGB1可上调TGF-β等炎症因子的表达，从而促进EMT的发生[21]。HMGB1还能诱导产生活性氧（reactive oxygen species, ROS）和细胞自噬，并通过ROS和细胞自噬促进细胞EMT[22]。由此可见，HMGB1能通过自噬反应、炎症反应和氧化应激等多种机制促进温石棉暴露诱导的EMT，具有重要的调控作用。
1.3 TNF-α
TNF-α是由巨噬细胞和单核细胞产生的多向性先导感染炎症因子，在许多病理状态下表达水平均会增加，如恶性肿瘤和慢性炎性疾病[23]。研究发现，长期暴露于温石棉环境或石棉肺患者体内的TNF-α含量明显高于健康人群[7]。其原因是温石棉长期暴露会诱导TNF-α过度表达，并且TNF-α可通过核转录因子（nuclear factor kappa-B, NF-κB）进一步促进温石棉与肺上皮细胞结合，使肺上皮细胞发生转化[24]。Qi等[25]发现，温石棉暴露分泌的TNF-α会使E-钙粘蛋白和β-连环蛋白表达减少，波形蛋白和α-平滑肌肌动蛋白（alpha-smooth muscle actin, α-SMA）表达增加，但此变化与温石棉暴露时长有关。说明TNF-α参与了温石棉诱发EMT的过程，并且EMT标志物在温石棉短期暴露时表达变化的持续性较短，需长期暴露才能为探讨EMT机制提供可靠依据。
1.4 IL
IL作为主要的炎症因子，在激活与调节免疫细胞及炎症反应中起重要作用。目前较多的研究者认为IL参与EMT过程，如IL-1β通过激活ZEB1基因、Snail-1蛋白等信号促进EMT，并且其促进分泌的IL-6也可诱导EMT[26]。此外，研究发现，温石棉暴露会促进IL-1β和IL-6等炎症因子表达。其中，温石棉通过自身激活、裂解炎症小体释放IL-1β，使体外正常的细胞发生EMT[27]。温石棉暴露也可通过分泌IL-6介导E盒结合锌指蛋白1（zinc finger E-box binding homeobox 1, ZEB1）、Snail-1等信号传导[4, 28]。ZEB1、Snail-1现已被证明参与EMT的发生发展，因此，IL可通过介导ZEB1、Snail-1的传导参与温石棉诱导的EMT。目前被发现参与温石棉诱导EMT过程的IL较少，以此为研究方向将为深入研究温石棉诱发与EMT相关的肺纤维化、癌症等疾病的作用机制提供新思路。
2. MAPK/ERK通路
MAPK是一组丝氨酸-苏氨酸蛋白激酶，经MAPK激酶和MAPK激酶激酶发生三级信号传递，共同调控细胞增殖、分化和肿瘤的侵袭、转移等生理活动[29]。在MAPK介导EMT的各种通路中，研究较广泛的是ERK通路。Papa等[30]研究显示，温石棉暴露会激活ERK，而ERK可经MAPK通路参与细胞的生长与分化。Tamminen等[31]发现，温石棉暴露可通过MAPK/ERK通路使A549细胞E-钙黏蛋白表达降低，α-SMA表达升高，使细胞间的连接减弱。这些说明温石棉可通过MAPK/ERK信号通路诱导细胞发生EMT。
此外，成纤维细胞生长因子（fibroblast growth factor, FGF）也可参与肺上皮细胞发生EMT的过程[32]。FGF与FGF受体（FGF receptor, FGFR）结合后形成二聚体并通过激酶结构域的磷酸化作用募集衔接蛋白激活下游信号传导，从而调节EMT的发生[33]。表皮生长因子（epidermal growth factor, EGF）与FGF作用相似，通过与受体结合激活信号传导，来促进细胞发生EMT[34]。研究显示，长期暴露于温石棉环境中，EGF、FGF及其受体的表达水平会发生变化并影响EMT过程[35-36]。通过蛋白质印迹法检测温石棉暴露后EGF受体（EGF receptor, EGFR）、磷酸化ERK1/2的表达水平，发现EGFR可使ERK磷酸化，从而激活MAPK/ERK通路[37]。说明FGF和EGF可通过MAPK/ERK通路介导温石棉暴露诱发EMT。
3. 其他调控机制
氧化应激与EMT密切相关。氧化应激是生物体受到刺激后，产生高水平、高活性物质，使机体氧化还原失衡并倾向于氧化的一种状态。氧化应激可通过调节细胞因子的表达及相关信号通路来影响EMT的进程[38-39]。其中，ROS作为氧化应激产生的高活性物质在此过程中发挥着重要作用。研究表明，温石棉暴露会使ROS积累，导致组织氧化损伤，并且机体氧化应激程度随温石棉暴露时间的延长而持续加深，从而促进EMT[40-41]。Sullivan等[42]发现，TNF-α和TGF-β1在温石棉诱导EMT过程中表达上调，并且TGF-β1可由ROS促进表达。由此说明，ROS不仅自身能促进温石棉诱导EMT，还可通过促进TGF-β1等转录因子的表达参与其中；并且温石棉经氧化应激发生EMT的程度与温石棉暴露时长有关。
发生EMT的其中一个标志是上皮细胞间的黏附被逐渐降解，而基质金属蛋白酶（matrix metalloproteinases, MMPs）进行蛋白水解正是此降解的主要因素。研究显示，温石棉暴露会诱导MMP-2[4]和MMP-7[43]等蛋白酶过度表达，其中作为EMT标志物的MMP-2被认为与TGF-β的相互调控是发生EMT的可能机制，并且MMP-7可促进MMP-2分泌。说明MMPs在温石棉暴露所致的EMT过程中发挥着一定作用。
4. 小结与展望
温石棉作为生活中广泛应用的矿物材料，与肺纤维化、肺癌和间皮瘤等疾病有着密切联系。研究者们通过研究炎症反应、MAPK途径和氧化应激等不同通路，发现了温石棉诱导EMT的新机制。然而，温石棉暴露引起EMT的机制研究仍有很多方面需要进一步探讨：（1）TNF-α和IL等炎症因子参与温石棉诱导EMT的结论主要集中在炎症因子会影响EMT标志物的表达水平，其具体调控机制尚未有研究说明，有待进一步研究；（2）现已知多种信号分子可通过不同的通路参与EMT过程，但目前针对温石棉诱导EMT仅TGF-β和MAPK/ERK相关通路被具体说明，其他通路的具体调控机制还有待探讨；（3）目前针对温石棉中ROS的研究，主要集中在其通过氧化应激诱导细胞凋亡，少见有研究关注ROS在温石棉诱导EMT中的具体机制；（4）温石棉由多种金属元素及二氧化硅组成，但目前对温石棉诱导EMT的研究均是从温石棉纤维整体出发，尚未有人从温石棉的组成成分来解释温石棉诱导EMT的机制，这有望成为一个新的研究点。综上所述，进一步研究温石棉诱导细胞发生EMT的具体机制，有望为温石棉致肺纤维化和肺癌等疾病的研究提供依据和参考。
-
[1] JIANG Z, CHEN J, CHEN J, et al. Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study[J]. Front Oncol, 2022, 12: 928839. doi: 10.3389/fonc.2022.928839
[2] LUBERTO F, FERRANTE D, SILVESTRI S, et al. Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy[J]. Environ Health, 2019, 18(1): 71. doi: 10.1186/s12940-019-0510-6
[3] JOLLY M K, WARD C, EAPEN M S, et al. Epithelial-mesenchymal transition, a spectrum of states: Role in lung development, homeostasis, and disease[J]. Dev Dyn, 2018, 247(3): 346-358. doi: 10.1002/dvdy.24541
[4] TURINI S, BERGANDI L, GAZZANO E, et al. Epithelial to mesenchymal transition in human mesothelial cells exposed to asbestos fibers: role of TGF-β as mediator of malignant mesothelioma development or metastasis via EMT event[J]. Int J Mol Sci, 2019, 20(1): 150. doi: 10.3390/ijms20010150
[5] ZHANG F, YUAN X, SUN H, et al. A nontoxic dose of chrysotile can malignantly transform Met-5A cells, in which microRNA-28 has inhibitory effects[J]. J Appl Toxicol, 2021, 41(11): 1879-1892. doi: 10.1002/jat.4174
[6] HELMIG S, WALTER D, PUTZIER J, et al. Oxidative and cytotoxic stress induced by inorganic granular and fibrous particles[J]. Mol Med Rep, 2018, 17(6): 8518-8529.
[7] BERNSTEIN D M, TOTH B, ROGERS R A, et al. Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL[J]. Toxicol Appl Pharmacol, 2020, 387: 114856. doi: 10.1016/j.taap.2019.114856
[8] FODDIS R, BONOTTI A, LANDI S, et al. Biomarkers in the prevention and follow-up of workers exposed to asbestos[J]. J Thorac Dis, 2018, 10(Suppl 2): S360-S368.
[9] ZI Z. Molecular engineering of the TGF-β signaling pathway[J]. J Mol Biol, 2019, 431(15): 2644-2654. doi: 10.1016/j.jmb.2019.05.022
[10] YAN X, XIONG X, CHEN Y G. Feedback regulation of TGF-β signaling[J]. Acta Biochim Biophys Sin, 2018, 50(1): 37-50. doi: 10.1093/abbs/gmx129
[11] TZAVLAKI K, MOUSTAKAS A. TGF-β Signaling[J]. Biomolecules, 2020, 10(3): 487. doi: 10.3390/biom10030487
[12] FRANGOGIANNIS N G. Transforming growth factor-β in tissue fibrosis[J]. J Exp Med, 2020, 217(3): e20190103. doi: 10.1084/jem.20190103
[13] SKULAND T, MASLENNIKOVA T, LÅG M, et al. Synthetic hydrosilicate nanotubes induce low pro-inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures[J]. Basic Clin Pharmacol Toxicol, 2020, 126(4): 374-388. doi: 10.1111/bcpt.13341
[14] GULINO G R, POLIMENI M, PRATO M, et al. Effects of Chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases[J]. Environ Health Perspect, 2016, 124(6): 776-784. doi: 10.1289/ehp.1409627
[15] QU J, ZHANG Z, ZHANG P, et al. Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT-mediated PF[J]. J Cell Physiol, 2019, 234(6): 8862-8872. doi: 10.1002/jcp.27548
[16] ZHANG Y, REN H, LI J, et al. Elevated HMGB1 expression induced by hepatitis B virus X protein promotes epithelial-mesenchymal transition and angiogenesis through STAT3/miR-34a/NF-κB in primary liver cancer[J]. Am J Cancer Res, 2021, 11(2): 479-494.
[17] GUI Y, SUN J, YOU W, et al. Glycyrrhizin suppresses epithelial-mesenchymal transition by inhibiting high-mobility group box1 via the TGF-β1/Smad2/3 pathway in lung epithelial cells[J]. Peer J, 2020, 8: e8514. doi: 10.7717/peerj.8514
[18] JIN J, GONG J, ZHAO L, et al. Inhibition of high mobility group box 1 (HMGB1) attenuates podocyte apoptosis and epithelial-mesenchymal transition by regulating autophagy flux[J]. J Diabetes, 2019, 11(10): 826-836. doi: 10.1111/1753-0407.12914
[19] HAO W, ZHU Y, GUO Y, et al. miR-1287-5p upregulation inhibits the EMT and pro-inflammatory cytokines in LPS-induced human nasal epithelial cells (HNECs)[J]. Transpl Immunol, 2021, 68: 101429. doi: 10.1016/j.trim.2021.101429
[20] HUANG W, YU C, LIANG S, et al. Long non-coding RNA TUG1 promotes airway remodeling and mucus production in asthmatic mice through the microRNA-181b/HMGB1 axis[J]. Int Immunopharmacol, 2021, 94: 107488. doi: 10.1016/j.intimp.2021.107488
[21] ZOLONDICK A A, GAUDINO G, XUE J, et al. Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review[J]. Precis Cancer Med, 2021, 4: 27. doi: 10.21037/pcm-21-12
[22] XUE J, PATERGNANI S, GIORGI C, et al. Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy[J]. Proc Natl Acad Sci USA, 2020, 117(41): 25543-25552. doi: 10.1073/pnas.2007622117
[23] VARFOLOMEEV E, VUCIC D. Intracellular regulation of TNF activity in health and disease[J]. Cytokine, 2018, 101: 26-32. doi: 10.1016/j.cyto.2016.08.035
[24] XIE C, REUSSE A, DAI J, et al. TNF-α increases tracheal epithelial asbestos and fiberglass binding via a NF-κB-dependent mechanism[J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(3): L608-L614. doi: 10.1152/ajplung.2000.279.3.L608
[25] QI F, OKIMOTO G, JUBE S, et al. Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling[J]. Am J Pathol, 2013, 183(5): 1654-1666. doi: 10.1016/j.ajpath.2013.07.029
[26] CHATTOPADHYAY I, AMBATI R, GUNDAMARAJU R. Exploring the crosstalk between inflammation and epithelial-mesenchymal transition in cancer[J]. Mediators Inflamm, 2021, 2021: 9918379.
[27] HILTBRUNNER S, MANNARINO L, KIRSCHNER M B, et al. Tumor immune microenvironment and genetic alterations in mesothelioma[J]. Front Oncol, 2021, 11: 660039. doi: 10.3389/fonc.2021.660039
[28] AINAGULOVA G, BULGAKOVA O, ILDERBAYEV O, et al. Molecular and immunological changes in blood of rats exposed to various doses of asbestos dust[J]. Cytokine, 2022, 159: 156016. doi: 10.1016/j.cyto.2022.156016
[29] GUO Y J, PAN W W, LIU S B, et al. ERK/MAPK signalling pathway and tumorigenesis[J]. Exp Ther Med, 2020, 19(3): 1997-2007.
[30] PAPA S, CHOY P M, BUBICI C. The ERK and JNK pathways in the regulation of metabolic reprogramming[J]. Oncogene, 2019, 38(13): 2223-2240. doi: 10.1038/s41388-018-0582-8
[31] TAMMINEN J A, MYLLÄRNIEMI M, HYYTIÄINEN M, et al. Asbestos exposure induces alveolar epithelial cell plasticity through MAPK/Erk signaling[J]. J Cell Biochem, 2012, 113(7): 2234-2247. doi: 10.1002/jcb.24094
[32] YANG L, ZHOU F, ZHENG D, et al. FGF/FGFR signaling: From lung development to respiratory diseases[J]. Cytokine Growth Factor Rev, 2021, 62: 94-104. doi: 10.1016/j.cytogfr.2021.09.002
[33] MOSSAHEBI-MOHAMMADI M, QUAN M, ZHANG J S, et al. FGF signaling pathway: a key regulator of stem cell pluripotency[J]. Front Cell Dev Biol, 2020, 8: 79. doi: 10.3389/fcell.2020.00079
[34] SABBAH D A, HAJJO R, SWEIDAN K. Review on epidermal growth factor receptor (EGFR) structure, signaling pathways, interactions, and recent updates of EGFR inhibitors[J]. Curr Top Med Chem, 2020, 20(10): 815-834. doi: 10.2174/1568026620666200303123102
[35] SCHELCH K, WAGNER C, HAGER S, et al. FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal[J]. Carcinogenesis, 2018, 39(4): 534-545. doi: 10.1093/carcin/bgy018
[36] YILMAZ S, DEMIRCI N Y, METINTAS S, et al. Effect of asbestos exposure on the frequency of EGFR mutations and ALK/ROS1 rearrangements in patients with lung adenocarcinoma: a multicentric study[J]. J Occup Environ Med, 2021, 63(3): 238-243. doi: 10.1097/JOM.0000000000002115
[37] GAETANI S, MONACO F, ALESSANDRINI F, et al. Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy[J]. Int J Biochem Cell Biol, 2020, 121: 105700. doi: 10.1016/j.biocel.2020.105700
[38] SONG Y, ZHANG W, ZHANG J, et al. TWIST2 inhibits EMT and induces oxidative stress in lung cancer cells by regulating the FGF21-mediated AMPK/mTOR pathway[J]. Exp Cell Res, 2021, 405(1): 112661. doi: 10.1016/j.yexcr.2021.112661
[39] RAMUNDO V, GIRIBALDI G, ALDIERI E. Transforming growth factor-β and oxidative stress in cancer: a crosstalk in driving tumor transformation[J]. Cancers (Basel), 2021, 13(12): 3093. doi: 10.3390/cancers13123093
[40] 黄柳雯, 崔琰, 查雨欣, 等. 温石棉和陶瓷纤维致大鼠炎症及氧化应激的毒性效应[J]. 岩石矿物学杂志, 2019, 38(6): 834-842. doi: 10.3969/j.issn.1000-6524.2019.06.012 HUANG L W, CUI Y, ZHA Y X, et al. Toxic effects of chrysotile asbestos and ceramic fibers on inflammation and oxidative stress in rats[J]. Acta Petrol Mineral, 2019, 38(6): 834-842. doi: 10.3969/j.issn.1000-6524.2019.06.012
[41] OKAZAKI Y. Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species[J]. Pathol Int, 2022, 72(2): 83-95. doi: 10.1111/pin.13196
[42] SULLIVAN D E, FERRIS M B, POCIASK D, et al. The latent form of TGFβ1 is induced by TNFα through an ERK specific pathway and is activated by asbestos-derived reactive oxygen species in vitro and in vivo[J]. J Immunotoxicol, 2008, 5(2): 145-149. doi: 10.1080/15476910802085822
[43] LEE S, YAMAMOTO S, SRINIVAS B, et al. Increased production of matrix metalloproteinase-7 (MMP-7) by asbestos exposure enhances tissue migration of human regulatory T-like cells[J]. Toxicology, 2021, 452: 152717. doi: 10.1016/j.tox.2021.152717
-
期刊类型引用(0)
其他类型引用(1)
计量
- 文章访问数: 103
- HTML全文浏览量: 18
- PDF下载量: 23
- 被引次数: 1
下载:
