Okrit Fatist, Chantranuwatana Poonchavist, Werawatganon Duangporn, Chayanupatkul Maneerat, Sanguanrungsirikul Sompol
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Heliyon. 2021 Jan 30;7(1):e05927. doi: 10.1016/j.heliyon.2021.e05927. eCollection 2021 Jan.
Cigarette smoke (CS) is a major cause of obstructive lung disease which is associated with significant disability and mortality. Vitamin D receptor (VDR) together with, mitogen activated protein kinases (MAPKs; ERK, JNK and p38) are the cellular transmission signals that mechanistically respond to CS and are recently found to have a role in lung pathogenesis. There are a few studies on subcellular VDR distribution involved MAPK but effects of cigarette smoke exposure with and without filter on this complex remain unclear. This study investigated subcellular VDR distribution and MAPK expression at early stages of both types of cigarette smoke exposure (CSE) in a rat model. Male Wistar rats were randomly divided into no-filter, filter and control groups. After 7 and 14 days of CSE, lung tissues were obtained to determine histopathology and protein expression. Cytoplasmic and nuclear VDR distribution significantly decreased on both CSE groups and corresponded with immunohistochemistry detection. The ratio of phosphorylated ERK to total ERK significantly increased in cytoplasm of both CSE on day 7. In particular, nuclear ERK MAPK significantly escalated in the filter group on day 14. In consistent with changes in intracellular markers, histopathological examination in both CSE groups showed significant increases in tracheal and peribronchiolar epithelial proliferation, alveolar macrophages and an increased trend of parenchymal infiltration. In summary, the evidence of lung injuries along with VDR depletion and MAPK activation observed in both CSE types indicated that there was no benefit of using cigarette filter to prevent protein damage or protect cells against cigarette smoke exposure in this model.
香烟烟雾(CS)是阻塞性肺病的主要病因,与严重的残疾和死亡率相关。维生素D受体(VDR)与丝裂原活化蛋白激酶(MAPKs;ERK、JNK和p38)一起,是对CS产生机械反应的细胞传导信号,最近发现它们在肺部发病机制中起作用。关于涉及MAPK的亚细胞VDR分布的研究较少,但有无过滤嘴的香烟烟雾暴露对这一复合体的影响仍不清楚。本研究在大鼠模型中调查了两种香烟烟雾暴露(CSE)早期的亚细胞VDR分布和MAPK表达。雄性Wistar大鼠随机分为无过滤嘴组、有过滤嘴组和对照组。CSE 7天和14天后,获取肺组织以确定组织病理学和蛋白表达。两个CSE组的细胞质和细胞核VDR分布均显著降低,与免疫组化检测结果一致。第7天时,两个CSE组细胞质中磷酸化ERK与总ERK的比率均显著升高。特别是,第14天时,有过滤嘴组细胞核中的ERK MAPK显著升高。与细胞内标志物的变化一致,两个CSE组的组织病理学检查均显示气管和细支气管周围上皮细胞增殖、肺泡巨噬细胞显著增加,实质浸润有增加趋势。总之,在两种CSE类型中观察到的肺损伤证据以及VDR耗竭和MAPK激活表明,在该模型中使用香烟过滤嘴对防止蛋白质损伤或保护细胞免受香烟烟雾暴露没有益处。