The interplay between TGF-β/SMAD and BMP/SMAD signaling pathways in the epithelial mesenchymal transition of A549 cells induced by silica

Abstract

The epithelial–mesenchymal transition (EMT) is a phenotype transdifferentiation of epithelial into mesenchymal cells and contributes to pulmonary fibrotic disease. SMAD-dependent pathway has been reported to play a key role in the multiple fibrotic diseases. We hypothesized that TGF-β/SMAD signaling could cross-interact with BMP/SMAD signaling pathways in silica-induced EMT in A549 cells. We investigated that the ability of silica-induced EMT in A549 cells, and this process was significantly inhibited by SB431542 through up-regulation of Vimentin, α-SMA and collagen type I expression and down-regulation of E-cadherin expression. Whereas BMP/SMAD inhibition using LDN193189 enhanced EMT. In addition, we also demonstrated that SB431542 could enhance BMP/SMAD signaling pathways in silica-induced EMT and vice versa. Therefore, our study provides evidence that the TGF-β/SMAD pathway was a crucial regulator in silica-induced EMT and that SB431542 could prevent the EMT. More importantly, we have identified that the interplay of TGF-β/SMAD and BMP/SMAD pathways in silica-induced EMT in A549 cells.

Keywords:

• Epithelial-mesenchymal transition
• silica
• TGF-β/SMAD pathway
• BMP/SMAD pathway

Disclosure statement

There is no conflict of interest.

Additional information

Funding

This work was supported by grants of National Natural Science Foundation of China (No. 81273047), Ministry of Science and Technology support project (No. 2012BAI15B08) and Key Project of National Communicable Disease (2012ZX10002015-002).