Changes of vitamin D receptors (VDR) and MAPK activation in cytoplasmic and nuclear fractions following exposure to cigarette smoke with or without filter in rats

Fatist Okrit,Poonchavist Chantranuwatana,Duangporn Werawatganon,Maneerat Chayanupatkul,Sompol Sanguanrungsirikul

doi:10.1016/j.heliyon.2021.e05927

Fatist Okrit, Poonchavist Chantranuwatana + Show 3 more

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https://doi.org/10.1016/j.heliyon.2021.e05927

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Journal: Heliyon	Publication Date: Jan 1, 2021
Citations: 8	License type: cc-by

Affiliation: Chulalongkorn University

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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 in vitro studies on subcellular VDR distribution involved MAPK but in vivo 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.

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Cigarette smoke is the major risk factor of chronic obstructive pulmonary disease (COPD) which is the third leading cause of mortality globally [1]
We attempted to explicate the effects of cigarette smoke exposure with and without filter on Vitamin D receptor (VDR) and Mitogen activated protein kinases (MAPKs) cascade distribution at the subcellular levels and its relation to lung pathogenesis by using a rat model that imitated human smoking behavior
Regardless of the filter, we found that cytoplasmic VDR expression decreased both at day 7 and day 14 of cigarette smoke exposure (CSE)

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Introduction

Cigarette smoke is the major risk factor of chronic obstructive pulmonary disease (COPD) which is the third leading cause of mortality globally [1]. Cigarette smoke is composed of more than 7,000 substances [2] which are associated with a wide variety of human pathologies, such as airway inflammation, COPD, atherosclerosis and age-related disorders [3]. Mitogen activated protein kinases (MAPKs) are intracellular molecules consisting of three subtypes, which are extracellular regulated kinase (ERK), stress activated protein kinase or c-Jun N-terminal kinase (JNK) and p38. All of these are involved in various cellular activities including cell proliferation, differentiation and cell survival [4]. These targets are located both in the cytoplasm and in the nucleus [5, 6, 7]

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