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硫芥诱导的人支气管气道中Smad分子的表达模式

Smad molecules expression pattern in human bronchial airway induced by sulfur mustard.

作者信息

Adelipour Maryam, Imani Fooladi Abbas Ali, Yazdani Samaneh, Vahedi Ensieh, Ghanei Mostafa, Nourani Mohammad Reza

机构信息

Chemical Injury Research Center (CIRC), Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2011 Sep;10(3):147-54.

PMID:21891820
Abstract

Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard lung patients. Mustard lung is the general description for the chronic obstructive pulmonary disease induced by sulfur mustard(SM). Pulmonary disease was diagnosed as the most important disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent developed during Wars. Iraqi forces frequently used it against Iranian during Iran -Iraq in the 1980-1988. Peribronchial fibrosis result from airway remodeling that include excess of collagen of extracellular matrix deposition in the airway wall. Some of Smads families in association with TGF-β are involved in airway remodeling due to lung fibrosis. In the present study we compared the mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall biopsies of chemical-injured patients with non-injured patients as control. We used airway wall biopsies of ten unexposed patients and fifteen SM-induced patients. Smads expression was evaluated by RT-PCR followed by bands densitometry. Expression levels of Smad3 and Smad4 in SM exposed patients were upregulated but Smad2 and Smad7 was not significantly altered. Our results revealed that Smad3, and 4 may be involved in airway remodeling process in SM induced patients by activation of TGF-β. Smad pathway is the most represented signaling mechanism for airway remodeling and peribronchial fibrosis. The complex of Smads in the nucleus affects a series of genes that results in peribronchial fibrosis in SM-induced patients.

摘要

气道重塑的特征是在芥子气肺患者中可见气道增厚和结构重组。芥子气肺是对由硫芥(SM)引起的慢性阻塞性肺疾病的统称。肺部疾病被诊断为接触硫芥个体中最重要的病症。硫芥是战争期间研制的一种化学战剂。在1980 - 1988年的两伊战争中,伊拉克军队经常对伊朗使用它。支气管周围纤维化是由气道重塑导致的,气道重塑包括气道壁细胞外基质中胶原蛋白过度沉积。一些与转化生长因子-β(TGF-β)相关的Smad家族参与了肺纤维化导致的气道重塑。在本研究中,我们比较了化学损伤患者气道壁活检组织与作为对照的未损伤患者气道壁活检组织中Smad2、Smad3、Smad4和Smad7基因的mRNA表达。我们使用了10名未接触者和15名硫芥诱导患者的气道壁活检组织。通过逆转录聚合酶链反应(RT-PCR)随后进行条带密度测定来评估Smads表达。硫芥暴露患者中Smad3和Smad4的表达上调,但Smad2和Smad7没有显著改变。我们的结果表明,Smad3和Smad4可能通过激活TGF-β参与硫芥诱导患者的气道重塑过程。Smad信号通路是气道重塑和支气管周围纤维化最典型的信号传导机制。细胞核中的Smads复合物影响一系列基因,导致硫芥诱导患者出现支气管周围纤维化。

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Smad molecules expression pattern in human bronchial airway induced by sulfur mustard.硫芥诱导的人支气管气道中Smad分子的表达模式
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引用本文的文献

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Long-term Respiratory Effects of Mustard Vesicants.芥子气类毒剂的长期呼吸系统效应。
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2
Evaluation of miR-9 and miR-143 expression in urine specimens of sulfur mustard exposed patients.芥子气暴露患者尿液样本中miR-9和miR-143表达的评估。
Interdiscip Toxicol. 2015 Dec;8(4):169-74. doi: 10.1515/intox-2015-0026.
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Mustard vesicant-induced lung injury: Advances in therapy.芥子气致肺损伤:治疗进展
Toxicol Appl Pharmacol. 2016 Aug 15;305:1-11. doi: 10.1016/j.taap.2016.05.014. Epub 2016 May 19.
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Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study.表观遗传学:硫芥气致肺损伤细胞和分子途径中缺失的范例:一项前瞻性比较研究
Iran J Basic Med Sci. 2015 Aug;18(8):723-36.
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Pathway reconstruction of airway remodeling in chronic lung diseases: a systems biology approach.慢性肺部疾病气道重塑的通路重建:一种系统生物学方法。
PLoS One. 2014 Jun 30;9(6):e100094. doi: 10.1371/journal.pone.0100094. eCollection 2014.
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Perspective in future pharmacological approach to sulfur mustard lung injuries.硫芥气致肺损伤未来药理学治疗方法的展望
J Res Med Sci. 2012 Nov;17(11):1092-3.
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Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase.硫芥肺损伤的治疗;从急性期到慢性期的新治疗方法。
Daru. 2012 Sep 10;20(1):27. doi: 10.1186/2008-2231-20-27.
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Inhalation of sulfur mustard causes long-term T cell-dependent inflammation: possible role of Th17 cells in chronic lung pathology.吸入芥子气会导致长期的 T 细胞依赖性炎症:Th17 细胞在慢性肺部病变中的可能作用。
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