Amygdalin alleviated TGF-β-induced epithelial-mesenchymal transition in bronchial epithelial cells

Transforming growth factor-beta TGF-β-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amygdalin, an active ingredient in bitter almonds, in TGF-β-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects. An asthmatic mouse model was established through ovalbumin induction. Primary mouse bronchial epithelial cells and a human bronchial epithelial cell line were incubated with transforming growth factor-beta (TGF-β) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE). In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expressions of EMT markers (α-SMA and vimentin). In TGF-β-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (α-SMA, vimentin, and fibronectin) without impairing cell viability. Through the Swiss Target Prediction database, HPSE was screened as a candidate downstream target for amygdalin. HPSE overexpression further promoted TGF-β-induced EMT while the HPSE inhibitor suppressed TGF-β-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-β-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination. Our study showed that amygdalin inhibited TGF-β-induced EMT in bronchial epithelial cells and found that the anti-EMT activity of amygdalin might be related to its regulatory effect on HPSE expression.