Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2.
Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2.
复制标题
抑制 Wnt/β-连环蛋白信号传导可通过减弱 TGF-β 1 和 FGF-2 的表达来抑制博来霉素诱导的肺纤维化
DOI：
10.1016/j.yexmp.2016.04.003
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发表时间：
2016-08
影响因子：
3.6
通讯作者：
Han, Xiaodong
中科院分区：
文献类型：
--
作者：
Chen, Xiang;Shi, Chaowen;Meng, Xiannan;Zhang, Kaijia;Li, Xiaoyao;Wang, Cong;Xiang, Zou;Hu, Kebin;Han, Xiaodong
关键词：
肺纤维化是一种病因不明的进行性肺部疾病，其特征在于肺泡上皮功能的改变、成纤维细胞活化和细胞外基质沉积增加。最近的研究表明，PF与肺损伤后细胞因子的不受控制的产生有关。在本研究中，我们发现转化生长因子-β1（TGF-β1）和成纤维细胞生长因子2（FGF-2）在博莱霉素诱导的纤维化肺组织和经博莱霉素处理的原代小鼠肺泡上皮II型（ATII）细胞中均上调。TGF-β1可诱导肺间充质干细胞（LR-MSCs）向成纤维细胞分化，这可能在肺纤维化中发挥重要作用。FGF-2可诱导LR-MSCs表达α-SMA和Vimentin。此外，在我们的研究中，我们发现Wnt/β-catenin信号转导在体外和体内都被博来霉素处理激活。有趣的是，我们还发现抑制Wnt/β-catenin信号通路可以显著减轻博莱霉素诱导的PF，同时降低TGF-β1和FGF-2在体外和体内的表达。这些结果支持通过抑制Wnt/β-catenin信号传导来控制TGF-β1和FGF-2的异常表达可以作为PF的潜在治疗策略。
Pulmonary fibrosis is a progressive lung disorder of unknown etiology, which is characterized by alterations in alveolar epithelium function, fibroblast activation, and increased extracellular matrix deposition. Recent studies have demonstrated that PF is associated with uncontrolled production of cytokines after lung injury. In the present study, we found that transforming growth factor-β1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) were both upregulated in bleomycin-induced fibrotic lung tissue and primary murine alveolar epithelial Type II (ATII) cells treated with bleomycin. Furthermore, we discovered that TGF-β1 could induce the differentiation of lung resident mesenchymal stem cells (LR-MSCs) into fibroblasts, which may play an essential role in PF. LR-MSCs incubated with FGF-2 showed modest alterations in the expression of α-SMA and Vimentin. Moreover, in our study, we found that Wnt/β-catenin signaling was activated both in vitro and in vivo as a result of bleomycin treatment. Interestingly, we also found that suppression of the Wnt/β-catenin signaling could significantly attenuate bleomycin-induced PF accompanied with decreased expression of TGF-β1 and FGF-2 in vitro and in vivo. These results support that controlling the aberrant expression of TGF-β1 and FGF-2 via inhibition of Wnt/β-catenin signaling could serve as a potential therapeutic strategy for PF.
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DOI：
10.4049/jimmunol.1302470
发表时间：
2014-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Le TT;Karmouty-Quintana H;Melicoff E;Le TT;Weng T;Chen NY;Pedroza M;Zhou Y;Davies J;Philip K;Molina J;Luo F;George AT;Garcia-Morales LJ;Bunge RR;Bruckner BA;Loebe M;Seethamraju H;Agarwal SK;Blackburn MR
通讯作者：
Blackburn MR
影响因子：
4.1
作者：
Kurayoshi, Manabu;Yamamoto, Hideki;Kikuchi, Akira
通讯作者：
Kikuchi, Akira
影响因子：
15.9
作者：
Jiang, Dianhua;Liang, Jiurong;Noble, Paul W.
通讯作者：
Noble, Paul W.
影响因子：
2.6
作者：
Chow K;Fessel JP;Kaoriihida-Stansbury;Schmidt EP;Gaskill C;Alvarez D;Graham B;Harrison DG;Wagner DH Jr;Nozik-Grayck E;West JD;Klemm DJ;Majka SM
通讯作者：
Majka SM
影响因子：
6
作者：
Chilosi, M;Poletti, V;Doglioni, C
通讯作者：
Doglioni, C