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

被引：10
作者：
Zhang, An-nan [1 ,2 ]
Li, Nan [1 ,2 ]
Chen, Zhuo-chang [1 ,2 ]
Guo, Ya-li [1 ,2 ]
Tian, Cui-jie [1 ,2 ]
Cheng, Dong-jun [1 ,2 ]
Tang, Xue-yi [1 ,2 ]
Zhang, Xiao-yu [1 ,2 ,3 ]
机构：
[1] Henan Prov Peoples Hosp, Dept Resp Dis & Intens Care, Zhengzhou, Peoples R China
[2] Zhengzhou Univ, Peoples Hosp, Dept Resp Dis & Intens Care, Zhengzhou, Peoples R China
[3] Henan Prov Peoples Hosp, Dept Resp Dis & Intens Care, 7 Weiwu Rd, Zhengzhou 450003, Peoples R China
来源：
CHEMICO-BIOLOGICAL INTERACTIONS | 2023年 / 369卷
基金：
中国国家自然科学基金;
关键词：
Amygdalin; Heparinase; Epithelial-mesenchymal transition; Bronchial epithelial cells; Asthma; HEPARANASE; ASTHMA;
D O I：
10.1016/j.cbi.2022.110235
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Objective: Transforming growth factor-beta TGF-beta-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amyg-dalin, an active ingredient in bitter almonds, in TGF-beta-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects.Methods: 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-beta) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (alpha-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE).Results: In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expres-sions of EMT markers (alpha-SMA and vimentin). In TGF-beta-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (alpha-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-beta-induced EMT while the HPSE inhibitor suppressed TGF-beta-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-beta-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination.Conclusion: Our study showed that amygdalin inhibited TGF-beta-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.
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页数：10
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