药学学报, 2021, 56(11): 2950-2956
引用本文:
朱含月, 朱媚, 陈喜华, 蒋小岗. 蓝萼甲素下调GSK3β/β-catenin信号通路抑制TGF-β1诱导的肺成纤维细胞转化[J]. 药学学报, 2021, 56(11): 2950-2956.
ZHU Han-yue, ZHU Mei, CHEN Xi-hua, JIANG Xiao-gang. Glaucocalyxin A represses TGF-β1-induced lung fibroblast differentiation by down-regulation of GSK3β/β-catenin signaling[J]. Acta Pharmaceutica Sinica, 2021, 56(11): 2950-2956.

蓝萼甲素下调GSK3β/β-catenin信号通路抑制TGF-β1诱导的肺成纤维细胞转化
朱含月1,2#, 朱媚1#, 陈喜华1, 蒋小岗1*
1. 苏州大学医学部药学院, 江苏 苏州 215000;
2. 无锡第二人民医院药学部, 江苏 无锡 214000
摘要:
本研究探讨了蓝萼甲素抑制转化生长因子-β1 (transforming growth factor-β1,TGF-β1) 诱导的肺成纤维细胞向肺肌成纤维细胞转化的作用及其分子机制。应用Western blot法、细胞免疫荧光法、胶原胶收缩法等检测蓝萼甲素抑制TGF-β1诱导的肺成纤维细胞转化指标的变化情况;应用Western blot法、质粒转染法、激活剂等考察蓝萼甲素对TGF-β1诱导的肺成纤维细胞转化中Smad3、细胞外信号调节激酶 (extracellular regulated protein kinases,ERK)、糖原合成酶激酶3β (glycogen synthase kinase 3β,GSK3β) (Ser9) 三者的磷酸化水平与β-连环蛋白 (β-catenin) 表达情况及其调控作用。结果表明: 蓝萼甲素能够显著降低肺成纤维细胞转化中α-平滑肌肌动蛋白 (α-smooth muscle actin,α-SMA) 表达水平;明显减少细胞肌丝的形成以及肺成纤维细胞胶原胶的收缩能力;显著下调纤维黏连蛋白 (fibronectin,FN) 的生成;不影响Smad3及ERK1/2的磷酸化水平;显著下调GSK3β (Ser9) 的磷酸化及β-catenin的表达水平;GSK3β (S9A) 突变体能明显抑制肺成纤维细胞转化;β-catenin激活剂SKL2001可部分逆转蓝萼甲素抑制肺成纤维细胞转化的作用。上述结果提示,蓝萼甲素能显著抑制肺成纤维细胞转化,这与蓝萼甲素下调GSK3β/β-catenin信号通路相关。
关键词:    肺纤维化      蓝萼甲素      肺成纤维细胞      转化生长因子-β1      糖原合成酶激酶3β/β-连环蛋白     
Glaucocalyxin A represses TGF-β1-induced lung fibroblast differentiation by down-regulation of GSK3β/β-catenin signaling
ZHU Han-yue1,2#, ZHU Mei1#, CHEN Xi-hua1, JIANG Xiao-gang1*
1. College of Pharmaceutical Sciences, School of Medicine, Soochow University, Suzhou 215000, China;
2. Department of Pharmacy, Wuxi No. 2 People's Hospital, Wuxi 214000, China
Abstract:
In this study, we investigated the effect and mechanism of glaucocalyxin A on transforming growth factor-β1 (TGF-β1)-induced differentiation of lung fibroblasts by Western blotting, cellular immunofluorescence and collagen gel contraction assays. We monitored the phosphorylation of Smad3, measured extracellular regulated protein kinases (ERK) 1/2 and glycogen synthase kinse3β (Ser9) activity and the level of β-catenin to elucidate the role of glaucocalyxin A. The results show that glaucocalyxin A significantly decreased the expression of α-smooth muscle actin in lung fibroblasts; glaucocalyxin A remarkably reduced the formation of filaments and collagen gel contraction of lung fibroblasts; glaucocalyxin A notably down-regulated the production of fibronectin; glaucocalyxin A did not affect the phosphorylation level of Smad3 and ERK1/2; glaucocalyxin A markedly inhibited the phosphorylation of GSK3β (Ser9) and the levels of β-catenin; a GSK3β (S9A) mutant significantly inhibited lung fibroblast differentiation; and SKL2001, a β-catenin activator, partly reversed the inhibition of lung fibroblast differentiation by glaucocalyxin A. These results suggest that glaucocalyxin A significantly inhibits the differentiation of lung fibroblasts, which is related to the down-regulation of GSK3β/β-catenin signaling.
Key words:    pulmonary fibrosis    glaucocalyxin A    lung fibroblast    transforming growth factor-β1    GSK3β/β-catenin   
收稿日期: 2021-06-02
DOI: 10.16438/j.0513-4870.2021-0819
基金项目: 国家自然科学基金资助项目(81573483).
通讯作者: 蒋小岗,Tel:86-512-65882090,E-mail:jiangxiaogang@suda.edu.cn
Email: jiangxiaogang@suda.edu.cn
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