Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression
ABSTRACT This study investigates the role of interleukin 6 antisense RNA 1 (IL6‐AS1), a highly expressed long noncoding RNA (lncRNA), in chronic obstructive pulmonary disease (COPD). An adeno‐associated virus (AAV) was used to induce the expression of IL6‐AS1 in mice, and they were exposed to cigare...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/mco2.70204 |
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| author | Erkang Yi Xiaoyu Wang Yu Liu Zihui Wang Ge Bai Xinyue Mei Fan Wu Chengshu Xie QiYang Li Weitao Cao Huahua Xu Xinyuan Liu Jieda Cui Haiqing Li Ruiting Sun Xinru Ran Wei Hong Zhishan Deng Bing Li Yumin Zhou Pixin Ran |
| author_facet | Erkang Yi Xiaoyu Wang Yu Liu Zihui Wang Ge Bai Xinyue Mei Fan Wu Chengshu Xie QiYang Li Weitao Cao Huahua Xu Xinyuan Liu Jieda Cui Haiqing Li Ruiting Sun Xinru Ran Wei Hong Zhishan Deng Bing Li Yumin Zhou Pixin Ran |
| author_sort | Erkang Yi |
| collection | DOAJ |
| description | ABSTRACT This study investigates the role of interleukin 6 antisense RNA 1 (IL6‐AS1), a highly expressed long noncoding RNA (lncRNA), in chronic obstructive pulmonary disease (COPD). An adeno‐associated virus (AAV) was used to induce the expression of IL6‐AS1 in mice, and they were exposed to cigarette smoke to establish a COPD model. IL6‐AS1‐overexpressing mice exposed to cigarette smoke demonstrated exacerbated COPD‐like pathologies. Integrated with single‐cell RNA sequencing analysis of COPD patients and pulmonary fibroblast–macrophage coculture system, our findings indicate that the upregulation of IL6‐AS1 in fibroblasts enhances the interaction between the S100A9 protein and the AGER and TLR4 receptors on lung macrophages, thereby exacerbating pulmonary inflammation. The molecular mechanism likely involves exosome‐mediated secretion, with IL6‐AS1 binding to S100A9 protein. These findings suggest that IL6‐AS1 may facilitate crosstalk between fibroblasts and macrophages, contributing to increased pulmonary inflammation, an effect that can be blocked by paquinimod. Mendelian randomization analysis further suggests a potential shared causal variant between IL6‐AS1 and COPD risk. Taken together, this investigation provides valuable insights into the function of IL6‐AS1 and its potential implications for the pathogenesis and therapeutic strategies in COPD. |
| format | Article |
| id | doaj-art-1b37c6b94f7242d8ac89e8814efe3db4 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-1b37c6b94f7242d8ac89e8814efe3db42025-08-20T03:39:28ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70204Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease ProgressionErkang Yi0Xiaoyu Wang1Yu Liu2Zihui Wang3Ge Bai4Xinyue Mei5Fan Wu6Chengshu Xie7QiYang Li8Weitao Cao9Huahua Xu10Xinyuan Liu11Jieda Cui12Haiqing Li13Ruiting Sun14Xinru Ran15Wei Hong16Zhishan Deng17Bing Li18Yumin Zhou19Pixin Ran20State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaGuangzhou National Laboratory. Guangzhou International BioIsland Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaGMU‐GIBH Joint School of Life Sciences Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaGMU‐GIBH Joint School of Life Sciences Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaABSTRACT This study investigates the role of interleukin 6 antisense RNA 1 (IL6‐AS1), a highly expressed long noncoding RNA (lncRNA), in chronic obstructive pulmonary disease (COPD). An adeno‐associated virus (AAV) was used to induce the expression of IL6‐AS1 in mice, and they were exposed to cigarette smoke to establish a COPD model. IL6‐AS1‐overexpressing mice exposed to cigarette smoke demonstrated exacerbated COPD‐like pathologies. Integrated with single‐cell RNA sequencing analysis of COPD patients and pulmonary fibroblast–macrophage coculture system, our findings indicate that the upregulation of IL6‐AS1 in fibroblasts enhances the interaction between the S100A9 protein and the AGER and TLR4 receptors on lung macrophages, thereby exacerbating pulmonary inflammation. The molecular mechanism likely involves exosome‐mediated secretion, with IL6‐AS1 binding to S100A9 protein. These findings suggest that IL6‐AS1 may facilitate crosstalk between fibroblasts and macrophages, contributing to increased pulmonary inflammation, an effect that can be blocked by paquinimod. Mendelian randomization analysis further suggests a potential shared causal variant between IL6‐AS1 and COPD risk. Taken together, this investigation provides valuable insights into the function of IL6‐AS1 and its potential implications for the pathogenesis and therapeutic strategies in COPD.https://doi.org/10.1002/mco2.70204chronic obstructive pulmonary diseaselncRNA interleukin 6 antisense RNA 1S100A9macrophagesMendelian randomization |
| spellingShingle | Erkang Yi Xiaoyu Wang Yu Liu Zihui Wang Ge Bai Xinyue Mei Fan Wu Chengshu Xie QiYang Li Weitao Cao Huahua Xu Xinyuan Liu Jieda Cui Haiqing Li Ruiting Sun Xinru Ran Wei Hong Zhishan Deng Bing Li Yumin Zhou Pixin Ran Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression MedComm chronic obstructive pulmonary disease lncRNA interleukin 6 antisense RNA 1 S100A9 macrophages Mendelian randomization |
| title | Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression |
| title_full | Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression |
| title_fullStr | Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression |
| title_full_unstemmed | Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression |
| title_short | Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression |
| title_sort | long noncoding rna interleukin 6 antisense rna 1 promotes inflammatory effects in lung macrophages via exosomes through the s100a9 tlr4 pathway in chronic obstructive pulmonary disease progression |
| topic | chronic obstructive pulmonary disease lncRNA interleukin 6 antisense RNA 1 S100A9 macrophages Mendelian randomization |
| url | https://doi.org/10.1002/mco2.70204 |
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