Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration
Abstract Background Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging. Methods Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-rel...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04228-x |
| _version_ | 1797801235617677312 |
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| author | Lingzi Wu Lei Zhou Jinying An Xianfeng Shao Hui Zhang Chunxi Wang Guixia Zhao Shuang Chen Xuexue Cui Xinyi Zhang Fuhua Yang Xiaorong Li Xiaomin Zhang |
| author_facet | Lingzi Wu Lei Zhou Jinying An Xianfeng Shao Hui Zhang Chunxi Wang Guixia Zhao Shuang Chen Xuexue Cui Xinyi Zhang Fuhua Yang Xiaorong Li Xiaomin Zhang |
| author_sort | Lingzi Wu |
| collection | DOAJ |
| description | Abstract Background Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging. Methods Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents. Results In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified. Conclusions This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents. |
| first_indexed | 2024-03-13T04:47:22Z |
| format | Article |
| id | doaj.art-501af1ac2ac3495e80d5808c0f45e2a2 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T04:47:22Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-501af1ac2ac3495e80d5808c0f45e2a22023-06-18T11:23:39ZengBMCJournal of Translational Medicine1479-58762023-06-0121112010.1186/s12967-023-04228-xComprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism explorationLingzi Wu0Lei Zhou1Jinying An2Xianfeng Shao3Hui Zhang4Chunxi Wang5Guixia Zhao6Shuang Chen7Xuexue Cui8Xinyi Zhang9Fuhua Yang10Xiaorong Li11Xiaomin Zhang12Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalDepartment of Applied Biology and Chemical Technology, School of Optometry, Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic UniversityTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of LifeomicsTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTangshan Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalTianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye HospitalAbstract Background Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging. Methods Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents. Results In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified. Conclusions This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents.https://doi.org/10.1186/s12967-023-04228-xPlasmaSmall extracellular vesiclesLarge extracellular vesiclesUveitisScleritisProteomic profiles |
| spellingShingle | Lingzi Wu Lei Zhou Jinying An Xianfeng Shao Hui Zhang Chunxi Wang Guixia Zhao Shuang Chen Xuexue Cui Xinyi Zhang Fuhua Yang Xiaorong Li Xiaomin Zhang Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration Journal of Translational Medicine Plasma Small extracellular vesicles Large extracellular vesicles Uveitis Scleritis Proteomic profiles |
| title | Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration |
| title_full | Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration |
| title_fullStr | Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration |
| title_full_unstemmed | Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration |
| title_short | Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration |
| title_sort | comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration |
| topic | Plasma Small extracellular vesicles Large extracellular vesicles Uveitis Scleritis Proteomic profiles |
| url | https://doi.org/10.1186/s12967-023-04228-x |
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