Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway
Diabetic retinopathy (DR) is a leading cause of blindness worldwide with limited treatment options. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) hold promise as a cell-free therapy for retinal diseases. In this study, we present evidence that the intravitreal injection of MS...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2024-03-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23003572 |
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| author | Fengtian Sun Yuntong Sun Xiaoling Wang Junyan Zhu Shenyuan Chen Yifan Yu Mengyao Zhu Wenrong Xu Hui Qian |
| author_facet | Fengtian Sun Yuntong Sun Xiaoling Wang Junyan Zhu Shenyuan Chen Yifan Yu Mengyao Zhu Wenrong Xu Hui Qian |
| author_sort | Fengtian Sun |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is a leading cause of blindness worldwide with limited treatment options. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) hold promise as a cell-free therapy for retinal diseases. In this study, we present evidence that the intravitreal injection of MSC-sEVs improved retinal function and alleviated retinal apoptosis, inflammation, and angiogenesis in both db/db mice and streptozotocin-induced diabetic rats. Mechanistically, hyperglycemia-induced activation of hypoxia-inducible factor-1α (HIF-1α) inhibited the tripartite motif 21 (TRIM21)-mediated ubiquitination and degradation of enhancer of zeste homologue 2 (EZH2), ultimately resulting in the downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) through EZH2-induced methylation modification. The presence of miR-5068 and miR-10228 in MSC-sEVs targeted the HIF-1α/EZH2/PGC-1α pathway. The blockade of miR-5068 and miR-10228 abolished the retinal therapeutic effects of MSC-sEVs. Additionally, we engineered MSC-sEVs with elevated levels of miR-5068 and miR-10228 to enhance retinal repair efficiency. Together, our findings provide novel insights into the mechanism underlying DR progress and highlight the potential of MSC-sEVs, especially engineered MSC-sEVs, as a therapeutic option for DR. |
| first_indexed | 2024-03-09T14:04:47Z |
| format | Article |
| id | doaj.art-5dc3bb7682334fc1bc2c5fe338a67e66 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-03-09T14:04:47Z |
| publishDate | 2024-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-5dc3bb7682334fc1bc2c5fe338a67e662023-11-30T05:08:09ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-03-0133444459Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathwayFengtian Sun0Yuntong Sun1Xiaoling Wang2Junyan Zhu3Shenyuan Chen4Yifan Yu5Mengyao Zhu6Wenrong Xu7Hui Qian8Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China; Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China; Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China; Department of Laboratory Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361006, Fujian, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China; Corresponding author. Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu, China.Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China; NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China; Corresponding author.Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301# Xuefu Road, Zhenjiang, 212013, Jiangsu, China.Diabetic retinopathy (DR) is a leading cause of blindness worldwide with limited treatment options. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) hold promise as a cell-free therapy for retinal diseases. In this study, we present evidence that the intravitreal injection of MSC-sEVs improved retinal function and alleviated retinal apoptosis, inflammation, and angiogenesis in both db/db mice and streptozotocin-induced diabetic rats. Mechanistically, hyperglycemia-induced activation of hypoxia-inducible factor-1α (HIF-1α) inhibited the tripartite motif 21 (TRIM21)-mediated ubiquitination and degradation of enhancer of zeste homologue 2 (EZH2), ultimately resulting in the downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) through EZH2-induced methylation modification. The presence of miR-5068 and miR-10228 in MSC-sEVs targeted the HIF-1α/EZH2/PGC-1α pathway. The blockade of miR-5068 and miR-10228 abolished the retinal therapeutic effects of MSC-sEVs. Additionally, we engineered MSC-sEVs with elevated levels of miR-5068 and miR-10228 to enhance retinal repair efficiency. Together, our findings provide novel insights into the mechanism underlying DR progress and highlight the potential of MSC-sEVs, especially engineered MSC-sEVs, as a therapeutic option for DR.http://www.sciencedirect.com/science/article/pii/S2452199X23003572Small extracellular vesiclesDiabetic retinopathyMesenchymal stem cellMiRNAEngineering |
| spellingShingle | Fengtian Sun Yuntong Sun Xiaoling Wang Junyan Zhu Shenyuan Chen Yifan Yu Mengyao Zhu Wenrong Xu Hui Qian Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway Bioactive Materials Small extracellular vesicles Diabetic retinopathy Mesenchymal stem cell MiRNA Engineering |
| title | Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway |
| title_full | Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway |
| title_fullStr | Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway |
| title_full_unstemmed | Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway |
| title_short | Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway |
| title_sort | engineered mesenchymal stem cell derived small extracellular vesicles for diabetic retinopathy therapy through hif 1α ezh2 pgc 1α pathway |
| topic | Small extracellular vesicles Diabetic retinopathy Mesenchymal stem cell MiRNA Engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23003572 |
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