Effect of the alteration of Tribbles homologue 3 expression on epithelial‑mesenchymal transition of transforming growth factor β1‑induced mouse alveolar epithelial cells through the Wnt/β‑catenin signaling pathway

Mol Med Rep. 2020 Feb;21(2):615-622. doi: 10.3892/mmr.2019.10863. Epub 2019 Dec 5.

Abstract

The aims of the present study were to elucidate the regulatory effect of exogenous Tribbles homologue 3 (TRB3) expression on the Wnt/β‑catenin signaling pathway and epithelial‑mesenchymal transition (EMT) in transforming growth factor‑β1 (TGF‑β1)‑induced mouse alveolar epithelial cells (MLE‑12) and investigate the underlying regulatory mechanisms. TRB3 expression was upregulated and downregulated using gene overexpression and RNA interference techniques, respectively. TGF‑β1‑stimulated MLE‑12 cells were examined for EMT and activation condition of the Wnt/β‑catenin signaling pathway using Cell Counting Kit‑8, flow cytometry, western blotting, reverse transcription‑quantitative PCR, ELISA and immunofluorescence techniques. During TGF‑β1‑induced EMT, TRB3 expression was found to be significantly upregulated (P<0.05). In the TRB3 overexpression group, upregulated expression of β‑catenin and EMT‑related genes and proteins was observed (P<0.05), and an increase in fibrosis‑related factors in the cell culture supernatant was detected (P<0.05); however, the results were the opposite in the TRB3 downregulated group (P<0.05). TRB3 may be involved in the regulation of EMT in TGF‑β1‑induced MLE‑12 cells through the Wnt/β‑catenin signaling pathway.

Keywords: epithelial-mesenchymal transition; idiopathic pulmonary fibrosis; transforming growth factor-β1; Tribbles homologue 3; Wnt/β-catenin signaling pathway.

MeSH terms

  • Actins / metabolism
  • Alveolar Epithelial Cells / drug effects
  • Alveolar Epithelial Cells / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Cadherins / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Proliferation / drug effects
  • Collagen / genetics
  • Collagen / metabolism
  • Epithelial-Mesenchymal Transition* / drug effects
  • Fibronectins / metabolism
  • Fluorescence
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • Vimentin / metabolism
  • Wnt Signaling Pathway* / drug effects
  • beta Catenin / metabolism

Substances

  • Actins
  • Cadherins
  • Cell Cycle Proteins
  • Fibronectins
  • RNA, Messenger
  • TRB3 protein, mouse
  • Transforming Growth Factor beta1
  • Vimentin
  • beta Catenin
  • Collagen