LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression
Abstract Diabetic retinopathy (DR) is a common complication of diabetes mellitus. Inflammatory responses play crucial roles in the progress of DR. Long noncoding RNA (lncRNAs) and microRNAs (miRNAs) are key signal transduction molecules in retina, and tightly connected with DR occurrence and develop...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-02-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12302 |
| _version_ | 1819059526413844480 |
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| author | Rong Luo Lan Li Yu‐Xiang Hu Fan Xiao |
| author_facet | Rong Luo Lan Li Yu‐Xiang Hu Fan Xiao |
| author_sort | Rong Luo |
| collection | DOAJ |
| description | Abstract Diabetic retinopathy (DR) is a common complication of diabetes mellitus. Inflammatory responses play crucial roles in the progress of DR. Long noncoding RNA (lncRNAs) and microRNAs (miRNAs) are key signal transduction molecules in retina, and tightly connected with DR occurrence and development. Our study aimed to explore the functions of lncRNA H19, miR‐19b and silence information regulator factor related enzymes 1 (SIRT1) in the progress of DR. Retinal pigment epithelial cells (ARPE‐19) were used to build high‐glucose (HG) model. Quantitative real‐time PCR (qPCR) was performed to detect expression of H19, miR‐19b and SIRT1 at normal glucose (NG) and HG conditions. And western blotting was performed to test protein level of SIRT1. QPCR and enzyme‐linked immunosorbent assay were performed to detect expression of inflammatory cytokines. Finally, the interactions among H19, miR‐19b and SIRT1 were determined by dual‐luciferase reporter assay. Our results showed that lncRNA H19 and SIRT1 were reduced, while miR‐19b was increased in ARPE‐19 cells with HG condition. MiR‐19b positively regulated the expression of inflammatory cytokines, including TNF‐α, IL‐1β and IL‐6. Inhibition of miR‐19b and overexpression of H19 inhibited the expression of inflammatory cytokines, such as TNF‐α, IL‐1β and IL‐6, while knockdown of SIRT1 reversed their effects on inflammatory cytokines. Furthermore, overexpression of miR‐19b reversed the inhibitory effects of overexpression of H19 on inflammatory cytokines. Importantly, H19 targeted miR‐19b to downregulate miR‐19b expression. Furthermore, miR‐19b bound to SIRT1 and declined SIRT1 expression. H19/miR‐19b/SIRT1 axis plays a key role of HG‐induced inflammatory response in ARPE‐19 cells, which provides new targets for DR treatment. |
| first_indexed | 2024-12-21T14:12:30Z |
| format | Article |
| id | doaj.art-527662c15a7449188c8958a098a16079 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-12-21T14:12:30Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-527662c15a7449188c8958a098a160792022-12-21T19:01:00ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502021-02-0137210111010.1002/kjm2.12302LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expressionRong Luo0Lan Li1Yu‐Xiang Hu2Fan Xiao3Department of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang ChinaDepartment of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang ChinaDepartment of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang ChinaDepartment of Ophthalmology Jiangxi Provincial People's Hospital Affiliated to Nanchang University Nanchang ChinaAbstract Diabetic retinopathy (DR) is a common complication of diabetes mellitus. Inflammatory responses play crucial roles in the progress of DR. Long noncoding RNA (lncRNAs) and microRNAs (miRNAs) are key signal transduction molecules in retina, and tightly connected with DR occurrence and development. Our study aimed to explore the functions of lncRNA H19, miR‐19b and silence information regulator factor related enzymes 1 (SIRT1) in the progress of DR. Retinal pigment epithelial cells (ARPE‐19) were used to build high‐glucose (HG) model. Quantitative real‐time PCR (qPCR) was performed to detect expression of H19, miR‐19b and SIRT1 at normal glucose (NG) and HG conditions. And western blotting was performed to test protein level of SIRT1. QPCR and enzyme‐linked immunosorbent assay were performed to detect expression of inflammatory cytokines. Finally, the interactions among H19, miR‐19b and SIRT1 were determined by dual‐luciferase reporter assay. Our results showed that lncRNA H19 and SIRT1 were reduced, while miR‐19b was increased in ARPE‐19 cells with HG condition. MiR‐19b positively regulated the expression of inflammatory cytokines, including TNF‐α, IL‐1β and IL‐6. Inhibition of miR‐19b and overexpression of H19 inhibited the expression of inflammatory cytokines, such as TNF‐α, IL‐1β and IL‐6, while knockdown of SIRT1 reversed their effects on inflammatory cytokines. Furthermore, overexpression of miR‐19b reversed the inhibitory effects of overexpression of H19 on inflammatory cytokines. Importantly, H19 targeted miR‐19b to downregulate miR‐19b expression. Furthermore, miR‐19b bound to SIRT1 and declined SIRT1 expression. H19/miR‐19b/SIRT1 axis plays a key role of HG‐induced inflammatory response in ARPE‐19 cells, which provides new targets for DR treatment.https://doi.org/10.1002/kjm2.12302ARPE‐19diabetic retinopathylncRNA H19miR‐19bSIRT1 |
| spellingShingle | Rong Luo Lan Li Yu‐Xiang Hu Fan Xiao LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression Kaohsiung Journal of Medical Sciences ARPE‐19 diabetic retinopathy lncRNA H19 miR‐19b SIRT1 |
| title | LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression |
| title_full | LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression |
| title_fullStr | LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression |
| title_full_unstemmed | LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression |
| title_short | LncRNA H19 inhibits high glucose‐induced inflammatory responses of human retinal epithelial cells by targeting miR‐19b to increase SIRT1 expression |
| title_sort | lncrna h19 inhibits high glucose induced inflammatory responses of human retinal epithelial cells by targeting mir 19b to increase sirt1 expression |
| topic | ARPE‐19 diabetic retinopathy lncRNA H19 miR‐19b SIRT1 |
| url | https://doi.org/10.1002/kjm2.12302 |
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