Autophagy in idiopathic pulmonary fibrosis.
Autophagy in idiopathic pulmonary fibrosis.
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DOI：
10.1371/journal.pone.0041394
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Morse D
中科院分区：
文献类型：
--
作者：
Patel AS;Lin L;Geyer A;Haspel JA;An CH;Cao J;Rosas IO;Morse D
自噬是一种基本的细胞内稳态过程，对细胞在应激条件下的命运决定非常重要。自噬的失调影响许多人类疾病，包括癌症和慢性阻塞性肺病。本研究探讨了自噬在特发性肺纤维化中的作用。使用蛋白质印迹、共聚焦显微镜和透射电子显微镜分析来自IPF患者的人肺组织的自噬标志物和调节蛋白。为研究TGF-β1对人肺成纤维细胞自噬的影响，采用荧光显微镜和Western blotting方法观察TGF-β1对人肺成纤维细胞自噬的影响。使用博来霉素诱导的纤维化小鼠模型进行体内实验。来自IPF患者的肺组织证明了通过LC 3、p62蛋白表达和免疫荧光以及自噬体数量评估的自噬活性降低的证据。TGF-β1至少部分通过激活mTORC 1在体外抑制成纤维细胞中的自噬; TIGAR的表达也响应TGF-β1而增加。在肺纤维化的博来霉素模型中，雷帕霉素治疗是抗纤维化的，并且雷帕霉素还在体外降低成纤维细胞的α-平滑肌肌动蛋白和纤连蛋白的表达。自噬的关键调节因子LC 3和beclin-1的抑制导致对α-平滑肌肌动蛋白和纤连蛋白的成纤维细胞表达的相反作用。自噬在肺纤维化中不被诱导，尽管已知促进自噬的途径被激活。TGF-β1对自噬的损害可能是促进IPF纤维化的一种机制。
Autophagy is a basic cellular homeostatic process important to cell fate decisions under conditions of stress. Dysregulation of autophagy impacts numerous human diseases including cancer and chronic obstructive lung disease. This study investigates the role of autophagy in idiopathic pulmonary fibrosis. Human lung tissues from patients with IPF were analyzed for autophagy markers and modulating proteins using western blotting, confocal microscopy and transmission electron microscopy. To study the effects of TGF-β1 on autophagy, human lung fibroblasts were monitored by fluorescence microscopy and western blotting. In vivo experiments were done using the bleomycin-induced fibrosis mouse model. Lung tissues from IPF patients demonstrate evidence of decreased autophagic activity as assessed by LC3, p62 protein expression and immunofluorescence, and numbers of autophagosomes. TGF-β1 inhibits autophagy in fibroblasts in vitro at least in part via activation of mTORC1; expression of TIGAR is also increased in response to TGF-β1. In the bleomycin model of pulmonary fibrosis, rapamycin treatment is antifibrotic, and rapamycin also decreases expression of á-smooth muscle actin and fibronectin by fibroblasts in vitro. Inhibition of key regulators of autophagy, LC3 and beclin-1, leads to the opposite effect on fibroblast expression of á-smooth muscle actin and fibronectin. Autophagy is not induced in pulmonary fibrosis despite activation of pathways known to promote autophagy. Impairment of autophagy by TGF-β1 may represent a mechanism for the promotion of fibrogenesis in IPF.
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影响因子：
3.9
作者：
Hwang, Jae-woong;Chung, Sangwoon;Sundar, Isaac K.;Yao, Hongwei;Arunachalam, Gnanapragasam;McBurney, Michael W.;Rahman, Irfan
通讯作者：
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作者：
ASHFORD, T P;PORTER, K R
通讯作者：
PORTER, K R
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作者：
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通讯作者：
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DOI：
10.1016/j.bbadis.2010.07.003
发表时间：
2011-01-01
影响因子：
6.2
作者：
Aranguiz-Urroz, Pablo;Canales, Jimena;Diaz-Araya, Guillermo
通讯作者：
Diaz-Araya, Guillermo