Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro

Fine particulate matter (PM2.5) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM2.5-induced ai...

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Main Authors: Huanhuan Zhu, Xiying Tang, Huilin Zhang, Meiyu Zhou, Hanting Liu, Haiyan Chu, Zhengdong Zhang
Format: Article
Language:English
Published: Elsevier 2023-04-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323002543
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author Huanhuan Zhu
Xiying Tang
Huilin Zhang
Meiyu Zhou
Hanting Liu
Haiyan Chu
Zhengdong Zhang
author_facet Huanhuan Zhu
Xiying Tang
Huilin Zhang
Meiyu Zhou
Hanting Liu
Haiyan Chu
Zhengdong Zhang
author_sort Huanhuan Zhu
collection DOAJ
description Fine particulate matter (PM2.5) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM2.5-induced airway obstruction. RNA sequencing revealed that acute PM2.5 exposure altered the expression profiles of 2904 exosomal circRNAs. Among them, exosomal hsa_circ_0029069 (spliced from CLIP1, thus termed circCLIP1 hereafter) with a loop structure was upregulated by PM2.5 exposure and mainly encapsulated in exosomes. Then, the biological functions and the underlying mechanisms were explored by Western blot, RNA immunoprecipitation and RNA pull-down, etc. Phenotypically, exosomal circCLIP1 entered recipient cells, inducing mucus secretion in recipient HBE cells and contractility of sensitive HBSMCs. Mechanistically, circCLIP1 was upregulated by METTL3-mediated N6-methyladenine (m6A) modification in PM2.5-treated producer HBE cells and exosomes, then enhancing the expression of SEPT10 in recipient HBE cells and sensitive HBSMCs. Our study revealed that exosomal circCLIP1 played a critical role in PM2.5-induced airway obstruction and provided a new potential biomarker for the assessment of PM2.5-related adverse effects.
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spelling doaj.art-1f8dbcaec3804f29bc3e395d001e8c5e2023-03-10T04:34:04ZengElsevierEcotoxicology and Environmental Safety0147-65132023-04-01254114750Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitroHuanhuan Zhu0Xiying Tang1Huilin Zhang2Meiyu Zhou3Hanting Liu4Haiyan Chu5Zhengdong Zhang6Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Correspondence to: Department of Environmental Genomics, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Jiangning District, Nanjing 211166, China.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Correspondence to: Department of Environmental Genomics, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Jiangning District, Nanjing 211166, China.Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; Correspondence to: Department of Environmental Genomics, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Jiangning District, Nanjing 211166, China.Fine particulate matter (PM2.5) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM2.5-induced airway obstruction. RNA sequencing revealed that acute PM2.5 exposure altered the expression profiles of 2904 exosomal circRNAs. Among them, exosomal hsa_circ_0029069 (spliced from CLIP1, thus termed circCLIP1 hereafter) with a loop structure was upregulated by PM2.5 exposure and mainly encapsulated in exosomes. Then, the biological functions and the underlying mechanisms were explored by Western blot, RNA immunoprecipitation and RNA pull-down, etc. Phenotypically, exosomal circCLIP1 entered recipient cells, inducing mucus secretion in recipient HBE cells and contractility of sensitive HBSMCs. Mechanistically, circCLIP1 was upregulated by METTL3-mediated N6-methyladenine (m6A) modification in PM2.5-treated producer HBE cells and exosomes, then enhancing the expression of SEPT10 in recipient HBE cells and sensitive HBSMCs. Our study revealed that exosomal circCLIP1 played a critical role in PM2.5-induced airway obstruction and provided a new potential biomarker for the assessment of PM2.5-related adverse effects.http://www.sciencedirect.com/science/article/pii/S0147651323002543Fine particulate matterExosomecircCLIP1Mucus secretionContractility
spellingShingle Huanhuan Zhu
Xiying Tang
Huilin Zhang
Meiyu Zhou
Hanting Liu
Haiyan Chu
Zhengdong Zhang
Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
Ecotoxicology and Environmental Safety
Fine particulate matter
Exosome
circCLIP1
Mucus secretion
Contractility
title Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
title_full Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
title_fullStr Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
title_full_unstemmed Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
title_short Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro
title_sort exosomal circclip1 regulates pm2 5 induced airway obstruction via targeting sept10 in vitro
topic Fine particulate matter
Exosome
circCLIP1
Mucus secretion
Contractility
url http://www.sciencedirect.com/science/article/pii/S0147651323002543
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