PMID- 34853720
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211203
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 26
DP  - 2021 Dec 3
TI  - Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in 
      high glucoseinjury and streptozotocin-induced diabetic mice.
PG  - 1201-1214
LID - 10.1016/j.omtn.2021.10.026 [doi]
AB  - 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.
CI  - (c) 2021 The Author(s).
FAU - Ge, Yanni
AU  - Ge Y
AD  - Department of Ophthalmology, The Second Xiangya Hospital, Central South 
      University, Changsha, Hunan 410011, China.
AD  - Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, 
      China.
FAU - Zhang, Ran
AU  - Zhang R
AD  - Department of Ophthalmology, The Second Xiangya Hospital, Central South 
      University, Changsha, Hunan 410011, China.
AD  - Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, 
      China.
FAU - Feng, Yuqing
AU  - Feng Y
AD  - Department of Ophthalmology, The Second Xiangya Hospital, Central South 
      University, Changsha, Hunan 410011, China.
AD  - Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, 
      China.
FAU - Lu, Jinfang
AU  - Lu J
AD  - Department of Ophthalmology, The Second Xiangya Hospital, Central South 
      University, Changsha, Hunan 410011, China.
AD  - Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, 
      China.
FAU - Li, Huiling
AU  - Li H
AD  - Department of Ophthalmology, The Second Xiangya Hospital, Central South 
      University, Changsha, Hunan 410011, China.
AD  - Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20211103
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC8605293
OTO - NOTNLM
OT  - Atf1
OT  - Mbd2
OT  - RGCs
OT  - apoptosis
OT  - diabetes
OT  - miR-345-5p
COIS- The authors declare no competing interests.
EDAT- 2021/12/03 06:00
MHDA- 2021/12/03 06:01
PMCR- 2021/11/03
CRDT- 2021/12/02 06:38
PHST- 2020/12/30 00:00 [received]
PHST- 2021/08/23 00:00 [revised]
PHST- 2021/10/29 00:00 [accepted]
PHST- 2021/12/02 06:38 [entrez]
PHST- 2021/12/03 06:00 [pubmed]
PHST- 2021/12/03 06:01 [medline]
PHST- 2021/11/03 00:00 [pmc-release]
AID - S2162-2531(21)00269-9 [pii]
AID - 10.1016/j.omtn.2021.10.026 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2021 Nov 3;26:1201-1214. doi: 10.1016/j.omtn.2021.10.026. 
      eCollection 2021 Dec 3.