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

Abstract

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.

Association of Smoking with the Blood Concentration of 25-Hydroxy Vitamin D and Testosterone at High and Low Altitudes

“…2 Similar to Grimnes et al, 6 we have reported that smoking at high altitude had an insignificant association with increased blood concentration of vitamin D. Moreover, this study found that smoking at a low altitude was associated with a significant decrease in the blood level of 25-HVD, similar to the findings of Ren et al, 4 Jiang et al, 5 and Lange et al 24 This may be due to the fact that cigarette smoke may affect expression levels of the vitamin D receptor. 25 This may also be due to decline in production of the 26 which was absent or delayed due to some unknown reasons at height, the reason for which is beyond the scope of this study. Also, reduced barometric pressures and excessive erythrocytosis encountered at higher altitudes might be also the reason for this increment of blood Vitamin D at high altitude due to some unknown mechanisms.…”

Induction mechanism of cigarette smoke components (CSCs) on dyslipidemia and hepatic steatosis in rats

“…The red dots represent the intestinal flora of the normal group, and the blue dots represent the CSC exposure group. There was a significant difference in the bacterial community between the normal control group and the CSC exposure group chemicals have been identified and determined in cigarettes [19]. To accurately and precisely identify these chemicals, the neutral, acidic, and alkaline chemicals of CSC were prepared and analyzed by GC-MS according to published literature [20].…”

“…Based on the preparation and characterization of cigarette smoke components (CSCs), this experiment carried out CSC exposure studies to explore the effects of CSCs on rat lipid metabolism levels and their underlying metabolic mechanisms. It is known that more than a thousand chemicals have been identified and determined in cigarettes [ 19 ]. To accurately and precisely identify these chemicals, the neutral, acidic, and alkaline chemicals of CSC were prepared and analyzed by GC–MS according to published literature [ 20 ].…”

Immunomodulatory Properties of Vitamin D in the Intestinal and Respiratory Systems

“…There is a paucity of information on the regulation of either lung or gut mucus secretion by vitamin D/VDR signaling. While bronchial and alveolar epithelial cells express VDR [ 34 , 39 ], whether bronchiole goblet/club cells express VDR or respond to vitamin D has not been addressed. There are two lines of evidence, albeit tenuous, implicating vitamin D/VDR signaling in colonic mucus secretion.…”