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circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica

Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO(2)-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO(2) on protein production and functio...

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Autores principales: Cao, Zhouli, Xiao, Qingling, Dai, Xiaoniu, Zhou, Zewei, Jiang, Rong, Cheng, Yusi, Yang, Xiyue, Guo, Huifang, Wang, Jing, Xi, Zhaoqing, Yao, Honghong, Chao, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870587/
https://www.ncbi.nlm.nih.gov/pubmed/29238093
http://dx.doi.org/10.1038/s41419-017-0017-4
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author Cao, Zhouli
Xiao, Qingling
Dai, Xiaoniu
Zhou, Zewei
Jiang, Rong
Cheng, Yusi
Yang, Xiyue
Guo, Huifang
Wang, Jing
Xi, Zhaoqing
Yao, Honghong
Chao, Jie
author_facet Cao, Zhouli
Xiao, Qingling
Dai, Xiaoniu
Zhou, Zewei
Jiang, Rong
Cheng, Yusi
Yang, Xiyue
Guo, Huifang
Wang, Jing
Xi, Zhaoqing
Yao, Honghong
Chao, Jie
author_sort Cao, Zhouli
collection PubMed
description Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO(2)-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO(2) 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 SiO(2). SiO(2) 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 SiO(2), inducing the development of silicosis. Inhibition of sigma-1 receptor ameliorated endoplasmic reticulum stress and fibroblast functional changes induced by SiO(2). circHIPK2 is involved in the regulation of sigma-1 receptor in human pulmonary fibroblasts-adult exposed to SiO(2). Our study elucidated a link between SiO(2)-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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spelling pubmed-58705872018-03-28 circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica Cao, Zhouli Xiao, Qingling Dai, Xiaoniu Zhou, Zewei Jiang, Rong Cheng, Yusi Yang, Xiyue Guo, Huifang Wang, Jing Xi, Zhaoqing Yao, Honghong Chao, Jie Cell Death Dis Article Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO(2)-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO(2) 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 SiO(2). SiO(2) 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 SiO(2), inducing the development of silicosis. Inhibition of sigma-1 receptor ameliorated endoplasmic reticulum stress and fibroblast functional changes induced by SiO(2). circHIPK2 is involved in the regulation of sigma-1 receptor in human pulmonary fibroblasts-adult exposed to SiO(2). Our study elucidated a link between SiO(2)-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. Nature Publishing Group UK 2017-12-13 /pmc/articles/PMC5870587/ /pubmed/29238093 http://dx.doi.org/10.1038/s41419-017-0017-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cao, Zhouli
Xiao, Qingling
Dai, Xiaoniu
Zhou, Zewei
Jiang, Rong
Cheng, Yusi
Yang, Xiyue
Guo, Huifang
Wang, Jing
Xi, Zhaoqing
Yao, Honghong
Chao, Jie
circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
title circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
title_full circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
title_fullStr circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
title_full_unstemmed circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
title_short circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
title_sort circhipk2-mediated σ-1r promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870587/
https://www.ncbi.nlm.nih.gov/pubmed/29238093
http://dx.doi.org/10.1038/s41419-017-0017-4
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