circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica.
circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica.
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circHIPK2介导的sigma-1R促进暴露于二氧化硅的人肺成纤维细胞的内质网应激
DOI：
10.1038/s41419-017-0017-4
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发表时间：
2017-12-13
影响因子：
9
通讯作者：
Chao J
中科院分区：
文献类型：
--
作者：
Cao Z;Xiao Q;Dai X;Zhou Z;Jiang R;Cheng Y;Yang X;Guo H;Wang J;Xi Z;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。尽管二氧化硅诱导肺泡巨噬细胞释放的趋化因子和细胞因子的作用已引起广泛关注，但对二氧化硅对肺成纤维细胞蛋白合成和功能变化的直接影响的研究较少。Sigma-1受体与中枢神经系统的细胞增殖和迁移有关，在肺中表达，但其在矽肺中的作用尚不清楚。为了阐明Sigma-1受体在二氧化硅诱导的肝纤维化中的作用，我们研究了Sigma-1受体对细胞增殖和迁移的上游分子机制和功能效应。应用分子生物学检测和药理学技术，结合迁移、增殖等功能实验，分析了二氧化硅对成人肺成纤维细胞分子和功能的影响。SiO_2诱导内质网应激与Sigma-1受体表达增强有关。内质网应激促进成人肺成纤维细胞的迁移和增殖，导致矽肺的发生。抑制Sigma-1受体可改善二氧化硅诱导的内质网应激和成纤维细胞功能改变。CircHIPK2参与调节暴露于二氧化硅的成人肺成纤维细胞中的Sigma-1受体。我们的研究阐明了二氧化硅诱导的纤维化和Sigma-1受体信号之间的联系，从而为Sigma-1受体/内质网应激在开发治疗矽肺的新治疗策略方面的潜在应用提供了新的见解。
Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO2-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO2 on protein production and functional changes in pulmonary fibroblasts have been less extensively studied. Sigma-1 receptor, which has been associated with cell proliferation and migration in the central nervous system, is expressed in the lung, but its role in silicosis remains unknown. To elucidate the role of sigma-1 receptor in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Both molecular biological assays and pharmacological techniques, combined with functional experiments, such as migration and proliferation, were applied in human pulmonary fibroblasts from adults to analyze the molecular and functional changes induced by SiO2. SiO2 induced endoplasmic reticulum stress in association with enhanced expression of sigma-1 receptor. Endoplasmic reticulum stress promoted migration and proliferation of human pulmonary fibroblasts-adult exposed to SiO2, inducing the development of silicosis. Inhibition of sigma-1 receptor ameliorated endoplasmic reticulum stress and fibroblast functional changes induced by SiO2. circHIPK2 is involved in the regulation of sigma-1 receptor in human pulmonary fibroblasts-adult exposed to SiO2. Our study elucidated a link between SiO2-induced fibrosis and sigma-1 receptor signaling, thereby providing novel insight into the potential use of sigma-1 receptor/endoplasmic reticulum stress in the development of novel therapeutic strategies for silicosis treatment.
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影响因子：
--
作者：
Kwon MJ;Kang SY;Nam ES;Cho SJ;Rho YS
通讯作者：
Rho YS
DOI：
10.1073/pnas.0402890101
发表时间：
2004-10-12
影响因子：
11.1
作者：
Hayashi, T;Su, TP
通讯作者：
Su, TP
影响因子：
5.1
作者：
Lenna S;Trojanowska M
通讯作者：
Trojanowska M
靶向配体的伴侣伴侣Sigma-1受体在神经精神疾病的治疗中。
影响因子：
5.8
作者：
Hayashi T;Tsai SY;Mori T;Fujimoto M;Su TP
通讯作者：
Su TP
影响因子：
4.6
作者：
Hsu HY;Lin TY;Lu MK;Leng PJ;Tsao SM;Wu YC
通讯作者：
Wu YC