Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation
Abstract Background Uveitis is a common recurrent autoimmune disease that seriously endangers the visual health of patients. MicroRNAs (miRNAs) are closely related to a series of autoimmune diseases. Methods The present study aimed to investigate the effect of miR-30b-5p on experimental autoimmune u...
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BMC
2025-04-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06438-x |
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| author | Xuewei Yin Huixia Wei Lijie Guo Bin Liu Yuan Peng Mengxian Zhou Yan Qiu Ruyi Qu Yane Gao Qiuxin Wu Wenjun Jiang Hongsheng Bi Dadong Guo |
| author_facet | Xuewei Yin Huixia Wei Lijie Guo Bin Liu Yuan Peng Mengxian Zhou Yan Qiu Ruyi Qu Yane Gao Qiuxin Wu Wenjun Jiang Hongsheng Bi Dadong Guo |
| author_sort | Xuewei Yin |
| collection | DOAJ |
| description | Abstract Background Uveitis is a common recurrent autoimmune disease that seriously endangers the visual health of patients. MicroRNAs (miRNAs) are closely related to a series of autoimmune diseases. Methods The present study aimed to investigate the effect of miR-30b-5p on experimental autoimmune uveitis (EAU) and its role in Notch signal activation as well as T helper (Th) cell differentiation, the relationship between miR-30b-5p levels and Notch signal activation, as well as Th cell differentiation in uveitis was further explored through flow cytometry, Immunohistochemistry immunofluorescence staining, PCR Array, and Ingenuity Pathway Analysis, and other technical methods to determine the fidelity of miR-30b-5p strategies in treating uveitis in vivo and in vitro. Results We demonstrated that ocular inflammation was significantly alleviated in EAU rats after miR-30b-5p intervention. miR-30b-5p could effectively inhibit Notch signaling activation and Th17 cell differentiation both in vitro and in vivo, and the Th17/Treg ratios were also notably decreased. Moreover, both Notch signaling and Th17 activation pathways were enriched and activated, in which Notch1 was the upstream regulatory molecule of Dll4 and IL-10 was an up-regulated upstream regulatory network molecule. Furthermore, miR-30b-5p could significantly reduce apoptosis in vitro, and clinical in vitro cell studies have shown that inactivating Notch pathway can improve the imbalance of Th17/Treg and cell apoptosis in T lymphocytes of patients with uveitis. Conclusions Together these studies identify that miR-30b-5p can significantly inhibit Notch signaling activation and Th17 cell differentiation, thereby restoring the Th17/Treg balance to treat uveitis, which may provide new insights into treating uveitis using miRNA interfering strategies. Graphical Abstract |
| format | Article |
| id | doaj-art-e16e0170602a4c558cf37ca7e3511c2e |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-e16e0170602a4c558cf37ca7e3511c2e2025-08-20T02:17:10ZengBMCJournal of Translational Medicine1479-58762025-04-0123112210.1186/s12967-025-06438-xTherapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activationXuewei Yin0Huixia Wei1Lijie Guo2Bin Liu3Yuan Peng4Mengxian Zhou5Yan Qiu6Ruyi Qu7Yane Gao8Qiuxin Wu9Wenjun Jiang10Hongsheng Bi11Dadong Guo12Shandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineGuangzhou Laboratory, Guangzhou Medical UniversityShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese Medicine Second Affiliated HospitalShandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineShandong Academy of Eye Disease Prevention and Therapy, Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineShandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular DiseasesAbstract Background Uveitis is a common recurrent autoimmune disease that seriously endangers the visual health of patients. MicroRNAs (miRNAs) are closely related to a series of autoimmune diseases. Methods The present study aimed to investigate the effect of miR-30b-5p on experimental autoimmune uveitis (EAU) and its role in Notch signal activation as well as T helper (Th) cell differentiation, the relationship between miR-30b-5p levels and Notch signal activation, as well as Th cell differentiation in uveitis was further explored through flow cytometry, Immunohistochemistry immunofluorescence staining, PCR Array, and Ingenuity Pathway Analysis, and other technical methods to determine the fidelity of miR-30b-5p strategies in treating uveitis in vivo and in vitro. Results We demonstrated that ocular inflammation was significantly alleviated in EAU rats after miR-30b-5p intervention. miR-30b-5p could effectively inhibit Notch signaling activation and Th17 cell differentiation both in vitro and in vivo, and the Th17/Treg ratios were also notably decreased. Moreover, both Notch signaling and Th17 activation pathways were enriched and activated, in which Notch1 was the upstream regulatory molecule of Dll4 and IL-10 was an up-regulated upstream regulatory network molecule. Furthermore, miR-30b-5p could significantly reduce apoptosis in vitro, and clinical in vitro cell studies have shown that inactivating Notch pathway can improve the imbalance of Th17/Treg and cell apoptosis in T lymphocytes of patients with uveitis. Conclusions Together these studies identify that miR-30b-5p can significantly inhibit Notch signaling activation and Th17 cell differentiation, thereby restoring the Th17/Treg balance to treat uveitis, which may provide new insights into treating uveitis using miRNA interfering strategies. Graphical Abstracthttps://doi.org/10.1186/s12967-025-06438-xExperimental autoimmune uveitisNotch signaling pathwaymiR-30b-5pTh cellNotch1Dll4 |
| spellingShingle | Xuewei Yin Huixia Wei Lijie Guo Bin Liu Yuan Peng Mengxian Zhou Yan Qiu Ruyi Qu Yane Gao Qiuxin Wu Wenjun Jiang Hongsheng Bi Dadong Guo Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation Journal of Translational Medicine Experimental autoimmune uveitis Notch signaling pathway miR-30b-5p Th cell Notch1 Dll4 |
| title | Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation |
| title_full | Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation |
| title_fullStr | Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation |
| title_full_unstemmed | Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation |
| title_short | Therapeutic effect of miR-30b-5p-loaded lentivirus on experimental autoimmune uveitis via inhibiting Notch signaling activation |
| title_sort | therapeutic effect of mir 30b 5p loaded lentivirus on experimental autoimmune uveitis via inhibiting notch signaling activation |
| topic | Experimental autoimmune uveitis Notch signaling pathway miR-30b-5p Th cell Notch1 Dll4 |
| url | https://doi.org/10.1186/s12967-025-06438-x |
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