Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8648555 | Molecular Immunology | 2018 | 9 Pages |
Abstract
Airway remodeling is a vital component of chronic obstructive pulmonary disease (COPD). Despite the broad anti-inflammation effects of glucocorticoids, they exhibit relatively little therapeutic benefit in COPD, indicating the accelerating demands of new agents for COPD. We aim to explore the effect of progesterone on airway remodeling in a murine modeling of exposing to ozone and to further examine the potential effect of progesterone on glucocorticoid insensitivity. C57/BL6 mice were exposed to ozone for 12 times over 6 weeks, and were administered with progesterone alone or combined with budesonide (BUD) after each exposure until the 10th week. The peribronchial collagen deposition was measured. The protein levels of MMP8 and MMP9 in bronchoalveolar lavage fluid (BALF) and lungs were assessed. Western blot analysis was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), a-smooth muscle actin (α-SMA), glycogen synthase kinase-3β (GSK-3β). The expression of VEGF and histone deacetylase 2 (HDAC2) in the lung were determined by Immunohistochemical analyses. We observe that progesterone attenuates the peribronchial collagen deposition, as well as the expression of MMP8, MMP9, HIF-1α, VEGF, α-SMA, and GSK-3β in BALF or lung tissues. Progesterone or BUD monotherapy has no effect on HDAC2 production. Progesterone combines with BUD induce dramatically enhanced effects. Thus, these results demonstrate novel roles of progesterone for the pathogenesis and airway remodeling in COPD. Progesterone plus BUD administration exerts more significant inhibition on airway remodeling with dose-independent. Additionally, progesterone may, to some extent, improve the glucocorticoid insensitivity.
Keywords
HIF-1αNF-κBα-SMAGSK-3βMMPPMSFASMTGF-β1HDAC2ICSPVDFECMMAPKROSenzyme linked immunosorbent assayAirway inflammationOzoneα-smooth muscle actininterleukinAirway remodelingBALFBudesonideCOPDChronic obstructive pulmonary diseaseTransforming growth factor-β1ELISAOxidative stressBudpolyvinylidene difluoridehypoxia-inducible factor-1αAirway smooth muscleVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)phenylmethylsulfonyl fluorideExtracellular matrixmatrix metalloproteinaseBronchoalveolar lavage fluidHistone deacetylase 2Western blotmitogen activated protein kinaseProgesteroneInhaled corticosteroidsGlycogen synthase kinase-3βReactive oxygen speciesglucocorticoid receptor
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Molecular Biology
Authors
Xue Zhang, Wuping Bao, Xia Fei, Yingying Zhang, Guoqing Zhang, Xin Zhou, Min Zhang,