Vitamin D modulates E-cadherin turnover by regulating TGF- and Wnt signalings during EMT-mediated myofibroblast differentiation in A459 cells
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Taşçı, Ahmet Erdal
Öztay, Füsün
Sarı, Ezgi
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Vitamin D (VitD) has an anti-fibrotic effect on fibrotic lungs. It reduces epithelial-mesenchymaltransition (EMT) on tumors. We aimed to investigate target proteins of VitD for the regression of EMTmediatedmyofibroblast differentiation. A group of A549 cells were treated with 5% cigarette smokeextract (CSE) and 5%CSE+TGF-β (5ng/ml) to induce EMT. The others were treated with 50 nM VitD30 min before %5CSE and TGF-β treatments. All cells were collected at 24, 48 and 72 hours following5%CSE and TGF-β administrations. The expression of p120ctn and NEDD9 proteins acted on Ecadherinturnover in addition to activations of TGF-β and Wnt pathways were examined in these cellsand fibrotic human lungs. CSE and TGF-β induced EMT by reducing E-cadherin, p-VDR, SMAD7 andDKK1, increasing α-SMA, p120ctn, Kaiso, NEDD9 and stimulating TGF-β and Wnt/β-cateninsignalings in A549 cells. VitD administration reversed these alterations and regressed EMT. Coimmunoprecipitationanalysis revealed p-VDR interaction with β-catenin and Kaiso in fibrotic and nonfibrotichuman lungs. VitD pre-treatments reduced TGF-β and Wnt/β-catenin signalings by increasingp-VDR, protected from E-cadherin degradation and led to the regression of EMT in A549 cells treatedwith CSE and TGF-β. Finally, VitD supplementation combined with anti-fibrotic therapeutics can besuggested for treatment of pulmonary fibrosis, which may be developed by smoking, in cases of VitDdeficiency.
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http://hdl.handle.net/20.500.12627/167594https://avesis.istanbul.edu.tr/api/publication/7d7fb6f5-367b-466a-8214-e52d4601452f/file
https://doi.org/10.1016/j.jsbmb.2020.105723
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