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

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.

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

“…TGF-β1 induces the expression of exogenous tribbles homolog 3 (TRB3), which stimulates EMT and promotes the onset of IPF. In addition, TRB3 may participate in the regulation of EMT in MLE-12 cells induced by TGF-β1 through the Wnt/β-catenin signaling pathway ( 97 ). Insulin-like growth factor-1 (IGF-I) can co-operate with TGF-β1 to enhance the proliferation of lung fibroblast ( 98 ).…”

Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway

“…In mouse type II alveolar epithelial cells (MLE-12), TGF-β induces TRB3 and depletion of TRB3 decreases of pSmad3 and fibrosis-related genes such as vimentin and fibronectin [ 94 ]. Additionally, TRB3 promotes EMT through the Wnt/β-catenin signaling pathway induced by TGF-β in MLE-12 cells [ 95 ]. Moreover bleomycin-induced pulmonary fibrosis in mice is regulated by TRB3 through activation of MAPK signaling [ 96 ].…”