LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy
PurposeDiabetic retinopathy (DR), a neurovascular disease, is one of the leading causes of blindness in working-age adults. Long noncoding RNAs (lncRNAs) have attracted attention as indicators for DR. This study aimed to characterize the role of lncRNA human testis development–related gene 1 (TDRG1)...
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01703/full |
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| author | Qiaoyun Gong Wenpei Dong Ying Fan Feng’e Chen Xiaolan Bian Xun Xu Tianwei Qian Tianwei Qian Ping Yu |
| author_facet | Qiaoyun Gong Wenpei Dong Ying Fan Feng’e Chen Xiaolan Bian Xun Xu Tianwei Qian Tianwei Qian Ping Yu |
| author_sort | Qiaoyun Gong |
| collection | DOAJ |
| description | PurposeDiabetic retinopathy (DR), a neurovascular disease, is one of the leading causes of blindness in working-age adults. Long noncoding RNAs (lncRNAs) have attracted attention as indicators for DR. This study aimed to characterize the role of lncRNA human testis development–related gene 1 (TDRG1) and its modulation of vascular endothelial growth factor (VEGF) in deteriorating DR.MethodsTissue samples were obtained from patients with epiretinal membranes (EMs) or proliferative DR, and human retinal microvascular endothelial cells (HRECs) were cultured with high-glucose medium to mimic DR as the in vitro model. The expression of lncRNA TDRG1 and VEGF was determined by immunofluorescence staining, Western blotting, and RT-qPCR. Transfection of small-interfering RNA was conducted to knock down target gene expression. HREC functions were evaluated by cell viability, fluorescein isothiocyanate (FITC)-dextran extravasation, migration, and tube formation assays under different conditions.ResultsLncRNA TDRG1 and VEGF were found to be co-expressed and significantly upregulated in fibrovascular membranes (FVMs) from DR patients compared to those from EM patients. In the in vitro model, hyperglycemic treatment markedly increased the expression of lncRNA TDRG1 and VEGF at the mRNA and protein levels, which promoted cell proliferation and migration, enhanced permeability, and disrupted tube formation of HRECs. However, knockdown of lncRNA TDRG1 or VEGF notably decreased the expression of VEGF and reversed the impaired functions of high-glucose-treated HRECs.ConclusionsLncRNA TDRG1 promoted microvascular cell dysfunction via upregulating VEGF in the progression of DR and may serve as a potential therapeutic target in DR treatment. |
| first_indexed | 2024-04-12T06:44:28Z |
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| language | English |
| last_indexed | 2024-04-12T06:44:28Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-1d888dff9b54487fb55d8649707352d22022-12-22T03:43:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-01-011010.3389/fphar.2019.01703496125LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic RetinopathyQiaoyun Gong0Wenpei Dong1Ying Fan2Feng’e Chen3Xiaolan Bian4Xun Xu5Tianwei Qian6Tianwei Qian7Ping Yu8Department of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaDepartment of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaDepartment of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaDepartment of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaDepartment of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaDepartment of Ophthalmology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaPurposeDiabetic retinopathy (DR), a neurovascular disease, is one of the leading causes of blindness in working-age adults. Long noncoding RNAs (lncRNAs) have attracted attention as indicators for DR. This study aimed to characterize the role of lncRNA human testis development–related gene 1 (TDRG1) and its modulation of vascular endothelial growth factor (VEGF) in deteriorating DR.MethodsTissue samples were obtained from patients with epiretinal membranes (EMs) or proliferative DR, and human retinal microvascular endothelial cells (HRECs) were cultured with high-glucose medium to mimic DR as the in vitro model. The expression of lncRNA TDRG1 and VEGF was determined by immunofluorescence staining, Western blotting, and RT-qPCR. Transfection of small-interfering RNA was conducted to knock down target gene expression. HREC functions were evaluated by cell viability, fluorescein isothiocyanate (FITC)-dextran extravasation, migration, and tube formation assays under different conditions.ResultsLncRNA TDRG1 and VEGF were found to be co-expressed and significantly upregulated in fibrovascular membranes (FVMs) from DR patients compared to those from EM patients. In the in vitro model, hyperglycemic treatment markedly increased the expression of lncRNA TDRG1 and VEGF at the mRNA and protein levels, which promoted cell proliferation and migration, enhanced permeability, and disrupted tube formation of HRECs. However, knockdown of lncRNA TDRG1 or VEGF notably decreased the expression of VEGF and reversed the impaired functions of high-glucose-treated HRECs.ConclusionsLncRNA TDRG1 promoted microvascular cell dysfunction via upregulating VEGF in the progression of DR and may serve as a potential therapeutic target in DR treatment.https://www.frontiersin.org/article/10.3389/fphar.2019.01703/fullLncRNA TDRG1vascular endothelial growth factorhyperglycemiahuman retinal microvascular endothelial cellsdiabetic retinopathy |
| spellingShingle | Qiaoyun Gong Wenpei Dong Ying Fan Feng’e Chen Xiaolan Bian Xun Xu Tianwei Qian Tianwei Qian Ping Yu LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy Frontiers in Pharmacology LncRNA TDRG1 vascular endothelial growth factor hyperglycemia human retinal microvascular endothelial cells diabetic retinopathy |
| title | LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy |
| title_full | LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy |
| title_fullStr | LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy |
| title_full_unstemmed | LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy |
| title_short | LncRNA TDRG1-Mediated Overexpression of VEGF Aggravated Retinal Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy |
| title_sort | lncrna tdrg1 mediated overexpression of vegf aggravated retinal microvascular endothelial cell dysfunction in diabetic retinopathy |
| topic | LncRNA TDRG1 vascular endothelial growth factor hyperglycemia human retinal microvascular endothelial cells diabetic retinopathy |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01703/full |
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