LIMR参与了AF-1对A549细胞上皮间质转化的抑制作用
刘伟^1,2, 唐四元¹, 万静³, 赵飞艳^2,2, 程庆梅², 黄晓婷^1,2, 李晨⁴, 罗自强^2,*
1中南大学湘雅护理学院，长沙 410000；²中南大学基础医学院，长沙 410000 ；³中南大学湘雅医院新生儿科，长沙 410000；⁴长治医学院基础医学部生理学教研室，长治 046000
摘要
肺泡上皮细胞发生上皮间质转化(epithelial-mesenchymal transition, EMT)是肺纤维化时肺内肌成纤维细胞的主要来源之一，在肺纤维化的发生和发展过程中具有重要作用。已有研究表明子宫珠蛋白(uteroglobin, UG)的活性片段antiflammin-1 (AF-1)能够有效地抑制博来霉素诱导的肺纤维化，然而，其作用机制尚未阐明。本研究利用细胞形态学检测和Western blot技术观察AF-1对转化生长因子β1 (transforming growth factor-β1, TGF-β1)诱导的A549细胞EMT的影响。结果显示，TGF-β1处理A549细胞后，α平滑肌肌动蛋白(α-smooth muscle actin, α-SMA)的表达明显上升而E-cadherin的表达显著下降，A549细胞由鹅卵石样上皮细胞向长梭形间质细胞转变。给予TGF-β1和AF-1共孵育细胞后，TGF-β1诱导A549细胞EMT的作用受到明显抑制。抗脂质运载蛋白相互作用膜受体(lipocalin interacting membrane receptor, LIMR)抗体或细胞外调节蛋白激酶(extracellular regulated protein kinases, ERK)信号通路阻断剂PD98059均能够减弱AF-1对TGF-β1诱导A549细胞EMT的抑制作用。上述结果表明，AF-1能够抑制TGF-β1诱导的A549细胞EMT转变，该作用有赖于LIMR及其下游ERK信号通路的参与。


关键词： 肺纤维化; 上皮间质转化; antiflammin-1; 脂质运载蛋白相互作用膜受体
分类号：R563

LIMR is involved in the inhibitory effect of antiflammin-1 on epithelial-mesenchymal transition in A549 cells
Liu Wei^1,2, TANG Si-Yuan¹, WAN Jing³, ZHAO Fei-Yan², CHENG Qing-Mei², HENG Qing-Mei², HUANG Xiao-Ting^1,2, LI Chen⁴, LUO Zi-Qiang^2,*
1iangya Nursing School, Central South University, Changsha 410000, China；²School of Basic Medical Science, Central South University, Changsha 410000, China；³Department of Neonatology, Xiangya Hospital, Central South University, Changsha 410000, China；⁴Department of Physiology, School of Basic Medical Science, Changzhi Medical College, Changzhi 046000, China
Abstract
Epithelial-mesenchymal transition (EMT) occurring in alveolar epithelial cells plays an important role in the development and progression of pulmonary fibrosis. Previous studies showed that antiflammin-1 (the active fragment of uteroglobin) effectively inhibited bleomycin-induced pulmonary fibrosis. However, its mechanism is still far from being clarified. In this study, we investigated the effects of antiflammin-1 on EMT in A549 cells induced by transforming growth factor-β1 (TGF-β1) and the underlying mechanism by using morphological observation and Western blot. The results showed that the expression of α-smooth muscle actin (α-SMA) increased significantly while the expression of E-cadherin decreased significantly in A549 cells following treatment with TGF-β1,concomitant with morphological change of A549 cells from pebble-like shape epithelial cells to spindle-like mesenchymal shape. This process of EMT in A549 cells induced by TGF-β1 was significantly inhibited when A549 cells were co-incubated with TGF-β1 and antiflammin-1. Furthermore, the anti-lipocalin interacting membrane receptor (LIMR) antibody and PD98059 (an ERK signaling pathway blocker) attenuated the inhibitory effect of antiflammin-1 on TGF-β1-induced EMT, respectively. Our findings indicate that antiflammin-1 can inhibit EMT in A549 cells induced by TGF-β1, which is related to LIMR and its downstream ERK signaling pathway.
Key words: pulmonary fibrosis; epithelial-mesenchymal transition; antiflammin-1; lipocalin interacting membrane receptor

收稿日期：2018-04-20　　录用日期：2018-08-23
通讯作者：罗自强　　E-mail: luozq1962@163.com
DOI: 10.13294/j.aps.2018.0057
引用本文：
刘伟, 唐四元, 万静, 赵飞艳, 程庆梅, 黄晓婷, 李晨, 罗自强. LIMR参与了AF-1对A549细胞上皮间质转化的抑制作用[J]. 生理学报 2018; 70 (5): 481-488.
Liu Wei, TANG Si-Yuan, WAN Jing, ZHAO Fei-Yan, CHENG Qing-Mei, HUANG Xiao-Ting, LI Chen, LUO Zi-Qiang. LIMR is involved in the inhibitory effect of antiflammin-1 on epithelial-mesenchymal transition in A549 cells. Acta Physiol Sin 2018; 70 (5): 481-488 (in Chinese with English abstract).



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