Inhibition of bleomycin-induced pulmonary fibrosis in mice by the novel peptide EZY-1 purified from Eucheuma
Inhibition of bleomycin-induced pulmonary fibrosis in mice by the novel peptide EZY-1 purified from Eucheuma
复制标题
麒麟菜中纯化的新型肽 EZY-1 对博莱霉素诱导的小鼠肺纤维化的抑制作用
DOI：
10.1039/c9fo00308h
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Zhang Haitao
中科院分区：
文献类型：
--
作者：
Yu Huajun;Zhang Zhao;Huang Hui;Wang Yajun;Lin Biyun;Wu Shang;Ma Jingyao;Chen Baoan;He Zhan;Wu Jun;Zhao Zuguo;Zhang Haitao
首次从麒麟菜中分离到一种新的16氨基酸多肽，命名为EZY-1。用EZY-1干预博莱霉素诱导的小鼠肺纤维化。采用体外下拉法结合LC-MS/MS筛选EZY-1的靶蛋白，结果表明EZY-1可以抑制博来霉素诱导的特发性肺纤维化（IPF）。EZY-1的效力和安全性上级于用于临床治疗的药物吡非尼酮。结果表明，EZY-1可抑制TGF-β/Smad、PI 3 K-Akt-mTOR、Rac 1-PAK 2-cAb 1和MAPK信号转导通路。在结合LC-MS/MS分析的体外下拉测定中，蛋白质如ERK、Akt、PDGF受体β、玻连蛋白、raptor和SHP 2显示出与EZY-1结合。EZY-1被证实是麒麟菜抑制IPF的有效成分。初步预测了EZY-1的信号通路和靶蛋白。本研究为麒麟菜治疗IPF的新药开发奠定了基础。
For the first time, a new 16-amino-acid peptide was isolated from Eucheuma, an edible seaweed, and named EZY-1. EZY-1 was used to interfere with bleomycin-induced mice pulmonary fibrosis. The target proteins of EZY-1 were screened by an in vitro pull-down method combined with LC-MS/MS. The results showed that EZY-1 can inhibit the idiopathic pulmonary fibrosis (IPF) induced by bleomycin. The potency and safety of EZY-1 are superior to those of the drug used for clinical treatment, pirfenidone. The results showed that EZY-1 suppresses the TGF-β/Smad, PI3K-Akt-mTOR, Rac1-PAK2-cAb1 and MAPK signal transduction pathways. Proteins such as ERK, Akt, PDGF receptor β, vitronectin, raptor and SHP2 exhibited binding to EZY-1 in an in vitro pull-down assay combined with LC-MS/MS analysis. EZY-1 was confirmed to be an effective component of Eucheuma in the inhibition of IPF. The signalling pathways and target proteins of EZY-1 were preliminarily predicted. This study lays the foundation for the development of new drugs from Eucheuma for the treatment of IPF.