Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction
Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectivel...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05034-9 |
| _version_ | 1797259057577328640 |
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| author | Wenhua Gan Wenwen Song Yujuan Gao Xuexue Zheng Fengjuan Wang Zirui Zhang Ke Zen Hongwei Liang Xin Yan |
| author_facet | Wenhua Gan Wenwen Song Yujuan Gao Xuexue Zheng Fengjuan Wang Zirui Zhang Ke Zen Hongwei Liang Xin Yan |
| author_sort | Wenhua Gan |
| collection | DOAJ |
| description | Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers. Methods In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments. Results Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model. Conclusion The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF. |
| first_indexed | 2024-04-24T23:03:23Z |
| format | Article |
| id | doaj.art-23cb39a8e4b14806bb851643516294f1 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-24T23:03:23Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-23cb39a8e4b14806bb851643516294f12024-03-17T12:36:46ZengBMCJournal of Translational Medicine1479-58762024-03-0122111110.1186/s12967-024-05034-9Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression predictionWenhua Gan0Wenwen Song1Yujuan Gao2Xuexue Zheng3Fengjuan Wang4Zirui Zhang5Ke Zen6Hongwei Liang7Xin Yan8Department of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of China Pharmaceutical UniversityDepartment of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Thoracic Surgery, Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical UniversityDepartment of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of China Pharmaceutical UniversityAbstract Background Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers. Methods In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments. Results Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model. Conclusion The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.https://doi.org/10.1186/s12967-024-05034-9Idiopathic pulmonary fibrosisExosomeCircular RNABiomarker |
| spellingShingle | Wenhua Gan Wenwen Song Yujuan Gao Xuexue Zheng Fengjuan Wang Zirui Zhang Ke Zen Hongwei Liang Xin Yan Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction Journal of Translational Medicine Idiopathic pulmonary fibrosis Exosome Circular RNA Biomarker |
| title | Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction |
| title_full | Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction |
| title_fullStr | Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction |
| title_full_unstemmed | Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction |
| title_short | Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction |
| title_sort | exosomal circrnas in the plasma serve as novel biomarkers for ipf diagnosis and progression prediction |
| topic | Idiopathic pulmonary fibrosis Exosome Circular RNA Biomarker |
| url | https://doi.org/10.1186/s12967-024-05034-9 |
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