Transforming growth factor-β1 (TGF-β1) associated epithelial-mesenchymal transition (EMT) contributes to multiple respiration diseases via Smad or MAPKs pathway. Our previous study has demonstrated that the typical macrolide antibiotic, azithromycin (AZM) played a notable anti-EMT role in ovalbumin (OVA)-challenged mice. However, the precise mechanism of AZM on TGF-β1 mediated EMT in bronchial epithelial cells is still unclear. The purpose of this study was to elucidate whether azithromycin targeting RACK1 inhibits TGF-β1 mediated EMT in vitro. The results showed that AZM significantly inhibited the expression of RACK1 and the activation of the downstream JNK, ERK, and Smad3 signaling pathways, thereby suppressing the migration of bronchial epithelial cells and reversing the TGF-β1-induced EMT. The effect of AZM on TGF-β1 mediated EMT in vitro is dependent on the dose of AZM. Although RACK1 has been shown to regulate IRE1α expression with siRACK1 transfection, there was no direct interaction between IRE1α and AZM. On the contrary, weak interaction between AZM and RACK1 was predicted with molecular docking. In summary, AZM targets RACK1 to trigger downstream JNK, ERK, and Smad3 signaling pathways and is an effective anti-EMT drug for bronchial epithelial cells in a dose-dependent manner.
Keywords: Azithromycin; Epithelial-mesenchymal transition; Molecular docking; RACK1/ TGF-β1.
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