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Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice.
- Source :
-
Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2021 Nov 03; Vol. 26, pp. 1201-1214. Date of Electronic Publication: 2021 Nov 03 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- DNA methylation is considered to play an important role in the development of diabetic retinopathy. Here, our goal was to investigate the precise role of methyl-CpG binding domain protein 2 (Mbd2) in the apoptosis of retinal ganglion cells (RGCs) in the early diabetic retina. Mbd2 was significantly upregulated after high glucose (HG) treatment and played a proapoptotic role in RGCs during HG-induced apoptosis. Combining ChIP and gene microarray datasets, the results showed that Mbd2 possessed potential binding sites for miR-345-5p, thereby elevating the expression levels of miR-345-5p via the enhancement of promoter demethylation. Activating transcription factor 1 (Atf1) played an anti-apoptotic role during the process of apoptosis in RGCs and acted as the target gene for miR-345-5p. Furthermore, the number of surviving RGCs in the diabetic retina was increased in Mbd2-knockout mice when compared with wild-type mice and the visual function became better accordingly. Collectively, our data demonstrated that the HG-induced overexpression of Mbd2 in the retina was partly responsible for the apoptosis of retinal neuronal cells through the miR-345-5p/Atf1 axis. Therefore, the targeting of Mbd2 might represent a novel therapeutic strategy for the treatment of neurodegeneration in the early diabetic retina.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2021 The Author(s).)
Details
- Language :
- English
- ISSN :
- 2162-2531
- Volume :
- 26
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Nucleic acids
- Publication Type :
- Academic Journal
- Accession number :
- 34853720
- Full Text :
- https://doi.org/10.1016/j.omtn.2021.10.026