ABSTRACT
BACKGROUND@#The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.@*METHODS@#Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.@*RESULTS@#Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.@*CONCLUSION@#1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.
ABSTRACT
<p><b>BACKGROUND</b>Psychological distress has been widely studied in many cardiovascular and pulmonary diseases, but the condition in acute pulmonary embolism (APE) is unknown. The purpose of this study was to investigate levels of depression and anxiety and their influencing factors in APE patients.</p><p><b>METHODS</b>Sixty consecutive patients with APE were subjected to investigation of depression and anxiety by the Beck Depression Inventory and State-Trait Anxiety Inventory, and 60 community-based subjects were enrolled as controls. APE patients were stratified as high-risk, intermediate-risk and low-risk according to the disease severity. Scores of depression and anxiety were compared by statistical analysis using paired t tests between APE patients and controls, and by analysis of variance within the APE patients with the three risk stratification. Factors influencing depression and anxiety were evaluated.</p><p><b>RESULTS</b>The mean age of the patients (38 males and 22 females) was (52 ± 12) years. APE patients displayed higher scores of depression (P = 0.04) and anxiety (P = 0.001) compared with controls. Patients in the high-risk group displayed higher scores of depression (P = 0.004) and anxiety (P = 0.001) compared with those in the intermediate- and low-risk groups. Depression scores were highly correlated with anxiety scores (r = 0.60, P < 0.001). Both depression and anxiety inversely related to risk stratification (P < 0.01), age (P < 0.05), and arterial blood oxygen pressure (PaO2) (P < 0.05). Linear regression analysis showed that PaO2 was independently inversely related to both depression (P < 0.01) and anxiety (P < 0.05); risk stratification and age were independently inversely related to anxiety (P < 0.05).</p><p><b>CONCLUSIONS</b>Patients of APE suffered high levels of depression and anxiety, which were negatively influenced by PaO2, risk stratification and age.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Age Factors , Anxiety , Diagnosis , Depression , Diagnosis , Pulmonary Embolism , Psychology , Sex Factors , Stress, PsychologicalABSTRACT
<p><b>BACKGROUND</b>The signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation.</p><p><b>METHODS</b>In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma.</p><p><b>RESULTS</b>In vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production.</p><p><b>CONCLUSION</b>These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.</p>