Vitamin D modulates E-cadherin turnover by regulating TGF-beta and Wnt signalings during EMT-mediated myofibroblast differentiation in A459 cells


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Sarı E., Öztay F. , Tasci A. E.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, cilt.202, 2020 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 202
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.jsbmb.2020.105723
  • Dergi Adı: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

Özet

Vitamin D (VitD) has an anti-fibrotic effect on fibrotic lungs. It reduces epithelial-mesenchymal transition (EMT) on tumors. We aimed to investigate target proteins of VitD for the regression of EMT-mediated myofibroblast differentiation. A group of A549 cells were treated with 5 % cigarette smoke extract (CSE) and 5 %CSE + TGF-beta (5 ng/ml) to induce EMT. The others were treated with 50 nM VitD 30 min before %5CSE and TGF-beta treatments. All cells were collected at 24, 48 and 72 h following 5 %CSE and TGF-beta administrations. The expression of p120ctn and NEDD9 proteins acted on E-cadherin turnover in addition to activations of TGF-beta and Wnt pathways were examined in these cells and fibrotic human lungs. CSE and TGF-beta induced EMT by reducing E-cadherin, p-VDR, SMAD7 and DKK1, increasing alpha-SMA, p120ctn, Kaiso, NEDD9 and stimulating TGF-beta and Wnt/beta-catenin signalings in A549 cells. VitD administration reversed these alterations and regressed EMT. Co-immunoprecipitation analysis revealed p-VDR interaction with beta-catenin and Kaiso in fibrotic and non-fibrotic human lungs. VitD pre-treatments reduced TGF-beta and Wnt/beta-catenin signalings by increasing p-VDR, protected from E-cadherin degradation and led to the regression of EMT in A549 cells treated with CSE and TGF-beta. Finally, VitD supplementation combined with anti-fibrotic therapeutics can be suggested for treatment of pulmonary fibrosis, which may be developed by smoking, in cases of VitD deficiency.