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
AIM:To investigate the expression of fatty-acid amide hydrolase(FAAH)in paraventricular nu-cleus(PVN)and its contribution to renal sympathetic nerve activity in rats with chronic heart failure(CHF).METH-ODS:A rat model of CHF was established by ligation of the left coronary artery to induce acute myocardial infarction. Eight weeks after ischemia,the rat model of CHF was identified by echocardiogram and histopathological observation.The plasma level of norepinephrine(NE)was detected by ELISA.The protein expression levels of FAAH in the PVN were de-termined by Western blot.The N-arachidonoylethanolamide(AEA)generation in PVN was analyzed by high-performance liquid chromatography.After microinjection of AEA,PF3845(an FAAH inhibitor)or rAAV2-FAAH shRNA virus in PVN, the sympathetic drive indexes were recorded in different experiment groups.RESULTS: Compared with the rats in sham group,the cardiac function and AEA concentration in PVN were significantly reduced, while the plasma NE level and FAAH expression in PVN were obviously increased in the CHF rats(P<0.05).After microinjecion of PF3845, AEA or rAAV2-FAAH shRNA virus in PVN, the sympathetic drive indexes were decreased significantly and the cardiac function were improved in the CHF rats.CONCLUSION:Upregulated FAAH expression in PVN may result in sympathoexcitation in the rat with CHF.