Calpain inhibition attenuates bleomycin-induced pulmonary fibrosis via switching the development of epithelial-mesenchymal transition.
Calpain inhibition attenuates bleomycin-induced pulmonary fibrosis via switching the development of epithelial-mesenchymal transition.
复制标题
钙蛋白酶抑制通过改变上皮间质转化的发展来减轻博来霉素诱导的肺纤维化
DOI：
10.1007/s00210-018-1499-z
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Cheng ZS
中科院分区：
文献类型：
--
作者：
Liu Y;Liu B;Zhang GQ;Zou JF;Zou ML;Cheng ZS
钙蛋白酶是一种细胞内钙依赖的半胱氨酸蛋白酶，可以分解几种底物蛋白，已被证明在肺纤维化中发挥重要作用。本研究旨在探讨钙蛋白酶对博莱霉素(BLM)诱导的肺纤维化的影响。通过腹腔注射博莱霉素成功建立了小鼠肺纤维化模型。CalPeptin是一种高度选择性的钙蛋白酶激活抑制剂，在博莱霉素注射后每周给药三次。组织学检查评估肝纤维化程度。用定量-聚合酶链式反应和免疫印迹法检测上皮-间充质转化(EMT)的发生。我们发现钙肽处理降低了博莱曼诱导的肌动蛋白(α-SMA)和I型胶原等肌动蛋白相关标志物，而增加了E-钙粘附素(E-cad)。钙肽还抑制转化生长因子β1-β2/3信号通路的激活，该信号通路在肺纤维化和内膜间质转化中起重要作用。此外，我们还发现，分化胚胎软骨细胞表达基因1(DEC1)是一种重要的转录因子，在特发性肺纤维化和博莱霉素诱导的肺纤维化中均上调。在博莱霉素诱导的小鼠模型中，钙肽对DEC1有抑制作用。综上所述，这些发现表明钙肽蛋白具有潜在的抗纤维化作用，这集中在EMT的发展上。
Calpains are intracellular calcium-dependent cysteine proteases, which cleave several substrates proteins, have been proven to play important roles in lung fibrosis. The aim of this study was to investigate the effects of calpain on bleomycin (BLM)-induced pulmonary fibrosis. A lung fibrosis mice model was established successfully by intraperitoneal injection of bleomycin. Calpeptin, a highly selective inhibitor of calpain activation, was administered three times weekly after bleomycin injection. Histological examination was used to assess the fibrosis. Quantitative-PCR and Western blotting were used to assess the development of epithelial-mesenchymal transition (EMT). We found calpeptin treatment decreased the BLM-induced EMT-associated markers, such as muscle actin (α-SMA) and collagen-I, while increased E-cadherin (E-cad). Calpeptin also suppressed the activation of transforming growth factor β1 (TGFβ1)-Smad2/3 signaling pathway, which plays crucial role in lung fibrosis and EMT. Furthermore, we found differentiated embryonic chondrocyte-expressed gene 1 (DEC1), an important transcription factor, was upregulated in both patients with idiopathic pulmonary fibrosis and in bleomycin-induced lung fibrosis. DEC1 was suppressed by calpeptin in bleomycin-induced mice model. Collectively, these findings indicated that calpeptin had a potential anti-fibrosis effect, which focus on the development of EMT.
登录
查看更多内容
悬浮在胶原蛋白凝胶中的上皮可以失去极性，并表达迁移间充质细胞的特征。
影响因子：
7.8
作者：
Greenburg, G;Hay, E D
通讯作者：
Hay, E D
DOI：
10.1161/hypertensionaha.112.196840
发表时间：
2012-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Jiang L;Zhang J;Monticone RE;Telljohann R;Wu J;Wang M;Lakatta EG
通讯作者：
Lakatta EG
影响因子：
8
作者：
Bertoli, C.;Copetti, T.;Schneider, C.
通讯作者：
Schneider, C.
影响因子：
4
作者：
Ikenouchi, J;Matsuda, M;Tsukita, S
通讯作者：
Tsukita, S
影响因子：
3.5
作者：
Rossner, MJ;Dorr, J;Nave, KA
通讯作者：
Nave, KA