Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury
Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120300469 |
| _version_ | 1818457314267496448 |
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| author | Yanni Ge Ran Zhang Yuqing Feng Huiling Li |
| author_facet | Yanni Ge Ran Zhang Yuqing Feng Huiling Li |
| author_sort | Yanni Ge |
| collection | DOAJ |
| description | Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells (RGCs) and Mbd2 knockout (Mbd2-KO) mice was used in the current study. We demonstrated that Mbd2 mediates RGC apoptosis caused by I/R injury. Mechanistically, the data suggested that Mbd2 upregulated Mbd2-associated long noncoding RNA 1 (Mbd2-AL1) via demethylation of its promoter. Furthermore, Mbd2-AL1 sponged microRNA (miR)-188-3p, thus preventing tumor necrosis factor (TNF) receptor-associated factor 3 (Traf3) downregulation and inducing RGC apoptosis. This was further demonstrated by the fact that inhibition of miR-188-3p diminished the anti-apoptosis role of Mbd2-AL1 small interfering RNA (siRNA). Finally, it showed that the apoptosis of retinal cells was attenuated, and the visual function was preserved in Mbd2-KO mice, which were associated with the Mbd2-AL1/miR-188-3p/Traf3 axis. Our present study revealed the role of Mbd2 in RGC apoptosis, which may provide a novel therapeutic strategy for retinal ischemic diseases. Keywords: Mbd2, lncRNA Mbd2-AL1, RGCs, apoptosis, miR-188-3p, retinal ischemia |
| first_indexed | 2024-12-14T22:40:36Z |
| format | Article |
| id | doaj.art-42aaa0bcdf114e0eb2dd0a0ca7d9fd16 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-14T22:40:36Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-42aaa0bcdf114e0eb2dd0a0ca7d9fd162022-12-21T22:44:59ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-03-011912501265Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion InjuryYanni Ge0Ran Zhang1Yuqing Feng2Huiling Li3Department of Ophthalmology in the Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, 410011 Hunan, ChinaDepartment of Ophthalmology in the Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, 410011 Hunan, ChinaDepartment of Ophthalmology in the Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, 410011 Hunan, ChinaDepartment of Ophthalmology in the Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, 410011 Hunan, China; Corresponding author: Huiling Li, MD, Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China.Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells (RGCs) and Mbd2 knockout (Mbd2-KO) mice was used in the current study. We demonstrated that Mbd2 mediates RGC apoptosis caused by I/R injury. Mechanistically, the data suggested that Mbd2 upregulated Mbd2-associated long noncoding RNA 1 (Mbd2-AL1) via demethylation of its promoter. Furthermore, Mbd2-AL1 sponged microRNA (miR)-188-3p, thus preventing tumor necrosis factor (TNF) receptor-associated factor 3 (Traf3) downregulation and inducing RGC apoptosis. This was further demonstrated by the fact that inhibition of miR-188-3p diminished the anti-apoptosis role of Mbd2-AL1 small interfering RNA (siRNA). Finally, it showed that the apoptosis of retinal cells was attenuated, and the visual function was preserved in Mbd2-KO mice, which were associated with the Mbd2-AL1/miR-188-3p/Traf3 axis. Our present study revealed the role of Mbd2 in RGC apoptosis, which may provide a novel therapeutic strategy for retinal ischemic diseases. Keywords: Mbd2, lncRNA Mbd2-AL1, RGCs, apoptosis, miR-188-3p, retinal ischemiahttp://www.sciencedirect.com/science/article/pii/S2162253120300469 |
| spellingShingle | Yanni Ge Ran Zhang Yuqing Feng Huiling Li Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury Molecular Therapy: Nucleic Acids |
| title | Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury |
| title_full | Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury |
| title_fullStr | Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury |
| title_full_unstemmed | Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury |
| title_short | Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury |
| title_sort | mbd2 mediates retinal cell apoptosis by targeting the lncrna mbd2 al1 mir 188 3p traf3 axis in ischemia reperfusion injury |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120300469 |
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