Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis
Abstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cart...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-03226-0 |
| _version_ | 1797397822449909760 |
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| author | Xiaonan Zhang Xiaoyu He Ming Zhang Tianyu Wu Xiaojie Liu Yan Zhang Zhuobei Xie Saisai Liu Tian Xia Yuanyuan Wang Fang Wei Hongtao Wang Changhao Xie |
| author_facet | Xiaonan Zhang Xiaoyu He Ming Zhang Tianyu Wu Xiaojie Liu Yan Zhang Zhuobei Xie Saisai Liu Tian Xia Yuanyuan Wang Fang Wei Hongtao Wang Changhao Xie |
| author_sort | Xiaonan Zhang |
| collection | DOAJ |
| description | Abstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. Methods The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. Results LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. Conclusions LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA. |
| first_indexed | 2024-03-09T01:16:41Z |
| format | Article |
| id | doaj.art-8bff66e59207448bbbb9387f9ba50d22 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-09T01:16:41Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-8bff66e59207448bbbb9387f9ba50d222023-12-10T12:27:08ZengBMCArthritis Research & Therapy1478-63622023-12-0125111510.1186/s13075-023-03226-0Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritisXiaonan Zhang0Xiaoyu He1Ming Zhang2Tianyu Wu3Xiaojie Liu4Yan Zhang5Zhuobei Xie6Saisai Liu7Tian Xia8Yuanyuan Wang9Fang Wei10Hongtao Wang11Changhao Xie12Bengbu Medical College Key Laboratory of Cardiovascular and Cerebrovascular DiseasesDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical CollegeBengbu Medical College Key Laboratory of Cardiovascular and Cerebrovascular DiseasesDepartment of Preventive Medicine, Bengbu Medical CollegeBengbu Medical College Key Laboratory of Cardiovascular and Cerebrovascular DiseasesClinical Medicine Department of Bengbu Medical CollegeDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical CollegeBengbu Medical College Key Laboratory of Cardiovascular and Cerebrovascular DiseasesClinical Medicine Department of Bengbu Medical CollegeDepartment of Tissue and Embryology, Bengbu Medical CollegeSchool of Pharmacy, Bengbu Medical CollegeAnhui Province Key Laboratory of Immunology in Chronic DiseasesDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical CollegeAbstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. Methods The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. Results LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. Conclusions LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.https://doi.org/10.1186/s13075-023-03226-0NanomedicineLncRNA LEF1-AS1miR-30-5pPIK3R2Rheumatoid arthritisSynovial fibroblasts |
| spellingShingle | Xiaonan Zhang Xiaoyu He Ming Zhang Tianyu Wu Xiaojie Liu Yan Zhang Zhuobei Xie Saisai Liu Tian Xia Yuanyuan Wang Fang Wei Hongtao Wang Changhao Xie Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis Arthritis Research & Therapy Nanomedicine LncRNA LEF1-AS1 miR-30-5p PIK3R2 Rheumatoid arthritis Synovial fibroblasts |
| title | Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis |
| title_full | Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis |
| title_fullStr | Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis |
| title_full_unstemmed | Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis |
| title_short | Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis |
| title_sort | efficient delivery of the lncrna lef1 as1 through the antibody lair 1 cd305 modified zn adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis |
| topic | Nanomedicine LncRNA LEF1-AS1 miR-30-5p PIK3R2 Rheumatoid arthritis Synovial fibroblasts |
| url | https://doi.org/10.1186/s13075-023-03226-0 |
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