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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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Detalles Bibliográficos
Autores principales: Ge, Yanni, Zhang, Ran, Feng, Yuqing, Li, Huiling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025978/
https://www.ncbi.nlm.nih.gov/pubmed/32074940
http://dx.doi.org/10.1016/j.omtn.2020.01.011
Descripción
Sumario: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.