circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1.
circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1.
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circHECTD1 通过 HECTD1 促进二氧化硅诱导的肺内皮-间质转化。
DOI：
10.1038/s41419-018-0432-1
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发表时间：
2018-03-14
影响因子：
9
通讯作者：
Chao J
中科院分区：
文献类型：
--
作者：
Fang S;Guo H;Cheng Y;Zhou Z;Zhang W;Han B;Luo W;Wang J;Xie W;Chao J
成纤维细胞的过度增殖和迁移导致矽肺肺纤维化，上皮细胞和内皮细胞分别通过上皮-间充质转化（EMT）和内皮-间充质转化（EndMT）参与成纤维细胞的聚集。将小鼠内皮细胞系（MML 1）暴露于二氧化硅（SiO2，50 μg/cm 2），并进行免疫荧光和蛋白质印迹分析，以评估特异性内皮和间充质标志物的水平，并阐明SiO2诱导EndMT的机制。通过分析细胞迁移和增殖来评价功能变化。使用qPCR和荧光原位杂交（FISH）测量mRNA和环状RNA（circRNA）水平。应用来自暴露于SiO2的Tie 2-GFP小鼠和硅肺患者的肺组织样品以确认来自体外实验的观察结果。基于当前研究的结果，SiO2增加了间充质标志物的表达，（I型胶原（COL 1A 1）、III型胶原（COL 3A 1）和α平滑肌肌动蛋白）（α-SMA/Acta 2）），并降低内皮标志物的表达（血管内皮钙粘蛋白（VE-Cad/Cdh 5）和血小板内皮细胞粘附分子-1（PECAM 1）），表明EndMT的发生响应于体内和体外的SiO2暴露。SiO2同时增加circHECTD 1的表达，这反过来又抑制HECTD 1蛋白的表达。SiO2诱导的细胞增殖，迁移和标志物水平变化的增加通过靶向circHECTD 1的小干扰RNA（siRNA）或通过CRISPR/Cas9系统过表达HECTD 1来恢复，证实了circHECTD 1/HECTD 1通路参与EndMT。此外，SiO2暴露小鼠和矽肺患者的组织样本证实了EndMT和HECTD 1表达的变化。我们的研究结果揭示了circHECTD 1/HECTD 1通路的潜在新功能，并提出了肺矽肺病患者纤维化的可能机制。
Excessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial–mesenchymal transition (EMT) and the endothelial–mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO2, 50 μg/cm2), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO2 induces the EndMT. Functional changes were evaluated by analyzing cell migration and proliferation. The mRNA and circular RNA (circRNA) levels were measured using qPCR and fluorescent in situ hybridization (FISH). Lung tissue samples from both Tie2-GFP mice exposed to SiO2 and silicosis patients were applied to confirm the observations from in vitro experiments. Based on the results from the current study, SiO2 increased the expression of mesenchymal markers (type I collagen (COL1A1), type III collagen (COL3A1) and alpha smooth muscle actin (α-SMA/Acta2)) and decreased the expression of endothelial markers (vascular endothelial cadherin (VE-Cad/Cdh 5) and platelet endothelial cell adhesion molecule-1 (PECAM1)), indicating the occurrence of the EndMT in response to SiO2 exposure both in vivo and in vitro. SiO2 concomitantly increased circHECTD1 expression, which, in turn, inhibited HECTD1 protein expression. SiO2-induced increases in cell proliferation, migration, and changes in marker levels were restored by either a small interfering RNA (siRNA) targeting circHECTD1 or overexpression of HECTD1 via the CRISPR/Cas9 system, confirming the involvement of the circHECTD1/HECTD1 pathway in the EndMT. Moreover, tissue samples from SiO2-exposed mice and silicosis patients confirmed the EndMT and change in HECTD1 expression. Our findings reveal a potentially new function for the circHECTD1/HECTD1 pathway and suggest a possible mechanism of fibrosis in patients with pulmonary silicosis.
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影响因子：
11.5
作者：
Choi, Seo-Hyun;Hong, Zhen-Yu;Lee, Yoon-Jin
通讯作者：
Lee, Yoon-Jin
影响因子：
4
作者：
Correia, Ana C. P.;Moonen, Jan-Renier A. J.;Krenning, Guido
通讯作者：
Krenning, Guido
影响因子：
3.9
作者：
Piera-Velazquez S;Mendoza FA;Jimenez SA
通讯作者：
Jimenez SA
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
影响因子：
9
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
通讯作者：
Chao J
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