Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy.
Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy.
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巨噬细胞衍生的 MCPIP1 通过自噬介导二氧化硅诱导的肺纤维化
DOI：
10.1186/s12989-016-0167-z
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发表时间：
2016-10-25
影响因子：
10
通讯作者：
Chao J
中科院分区：
文献类型：
--
作者：
Liu H;Fang S;Wang W;Cheng Y;Zhang Y;Liao H;Yao H;Chao J
矽肺的特征是成纤维细胞堆积和细胞外基质过度沉积。单核细胞趋化蛋白-1诱导蛋白1(MCPIP1)在二氧化硅诱导的肝纤维化中起重要作用。然而，肺纤维化中MCPIP1活性下游事件的细节仍不清楚。为了阐明MCPIP1诱导的自噬在SiO_2诱导的纤维化中的作用，我们研究了SiO_2诱导细胞凋亡、增殖和迁移的上游分子机制和功能效应。利用原代培养的健康人和矽肺患者的肺泡巨噬细胞以及分化的U937巨噬细胞的实验结果表明：1)SiO_2诱导巨噬细胞自噬并伴随MCPIP1表达的增强；2)自噬促进暴露于SiO_2的巨噬细胞的凋亡和激活，这些事件导致矽肺的发生；3)MCPIP1通过P53信号介导的自噬促进巨噬细胞的凋亡和激活；以及4)SiO_2激活的巨噬细胞通过MCPIP1/P53介导的自噬途径促进成纤维细胞的增殖和迁移。我们的结果阐明了二氧化硅诱导的纤维化和MCPIP1/P53信号介导的自噬之间的联系。这些发现为MCPIP1或自噬在开发潜在的矽肺治疗策略中的潜在靶向提供了新的见解。本文的在线版本(doi：10.1186/s12989-01670167-z)包含补充材料，授权用户可以使用。
Silicosis is characterized by accumulation of fibroblasts and excessive deposition of extracellular matrix. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a critical role in fibrosis induced by SiO2. However, the details of the downstream events of MCPIP1 activity in pulmonary fibrosis remain unclear. To elucidate the role of MCPIP1-induced autophagy in SiO2-induced fibrosis, both the upstream molecular mechanisms and the functional effects of SiO2 on cell apoptosis, proliferation and migration were investigated. Experiments using primary cultures of alveolar macrophages from healthy donors and silicosis patients as well as differentiated U937 macrophages demonstrated the following results: 1) SiO2 induced macrophage autophagy in association with enhanced expression of MCPIP1; 2) autophagy promoted apoptosis and activation of macrophages exposed to SiO2, and these events induced the development of silicosis; 3) MCPIP1 facilitated macrophage apoptosis and activation via p53 signaling-mediated autophagy; and 4) SiO2-activated macrophages promoted the proliferation and migration of fibroblasts via the MCPIP1/p53-mediated autophagy pathway. Our results elucidated a link between SiO2-induced fibrosis and MCPIP1/p53 signaling-mediated autophagy. These findings provide novel insight into the potential targeting of MCPIP1 or autophagy in the development of potential therapeutic strategies for silicosis. The online version of this article (doi:10.1186/s12989-016-0167-z) contains supplementary material, which is available to authorized users.
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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：
Rahman, Irfan
MCPIP1 调节 MAP 激酶和 NF-kappaB 下游 3-D 胶原基质中成纤维细胞的迁移。
DOI：
10.1038/jid.2015.334
发表时间：
2015-12
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Chao J;Dai X;Peña T;Doyle DA;Guenther TM;Carlson MA
通讯作者：
Carlson MA
影响因子：
13.3
作者：
Crighton, Diane;Wilkinson, Simon;Ryan, Kevin M.
通讯作者：
Ryan, Kevin M.
自噬对于超细颗粒诱导的气道上皮炎症和粘液过度产生至关重要
影响因子：
13.3
作者：
Chen, Zhi-Hua;Wu, Yin-Fang;Shen, Hua-Hao
通讯作者：
Shen, Hua-Hao
影响因子：
8.3
作者：
BENSON, SC;BELTON, JC;SCHEVE, LG
通讯作者：
SCHEVE, LG