Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice

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...

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Autores principales:	Yanni Ge, Ran Zhang, Yuqing Feng, Jinfang Lu, Huiling Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Mbd2 miR-345-5p RGCs apoptosis diabetes Atf1 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/cd04554a343e4be0af15531405bb3830
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spelling	oai:doaj.org-article:cd04554a343e4be0af15531405bb38302021-11-20T05:05:34ZMbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice2162-253110.1016/j.omtn.2021.10.026https://doaj.org/article/cd04554a343e4be0af15531405bb38302021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002699https://doaj.org/toc/2162-2531DNA 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.Yanni GeRan ZhangYuqing FengJinfang LuHuiling LiElsevierarticleMbd2miR-345-5pRGCsapoptosisdiabetesAtf1Therapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1201-1214 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mbd2 miR-345-5p RGCs apoptosis diabetes Atf1 Therapeutics. Pharmacology RM1-950
spellingShingle	Mbd2 miR-345-5p RGCs apoptosis diabetes Atf1 Therapeutics. Pharmacology RM1-950 Yanni Ge Ran Zhang Yuqing Feng Jinfang Lu Huiling Li Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
description	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.
format	article
author	Yanni Ge Ran Zhang Yuqing Feng Jinfang Lu Huiling Li
author_facet	Yanni Ge Ran Zhang Yuqing Feng Jinfang Lu Huiling Li
author_sort	Yanni Ge
title	Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
title_short	Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
title_full	Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
title_fullStr	Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
title_full_unstemmed	Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
title_sort	mbd2 deficiency alleviates retinal cell apoptosisvia the mir-345-5p/atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/cd04554a343e4be0af15531405bb3830
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Mbd2 deficiency alleviates retinal cell apoptosisvia the miR-345-5p/Atf1 axis in high glucoseinjury and streptozotocin-induced diabetic mice

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