Evidence map›Paper›PMID 40380281›Full record

ArticleClinical epigenetics2025

DNA hypermethylation of PLTP mediated by DNMT3B aggravates vascular dysfunction in diabetic retinopathy via the AKT/GSK3β signaling pathway.

Chunyang Cai, Chufeng Gu, Chunren Meng, Yujie Wang, Qingquan Wei, Shuai He, Dongwei Lai, Xingyun Wang, Tengfei Wang, Qinghua Qiu

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Chunyang Cai *Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Chufeng Gu *Department of Ophthalmology, Fuzhou University Affiliated Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China. guchufeng@fjsl.com.cn.
Chunren Meng *Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
Yujie Wang *Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
Qingquan WeiDepartment of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Shuai HeDepartment of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Dongwei LaiDepartment of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Xingyun WangHongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. wxy@shsmu.edu.cn.
Tengfei WangDepartment of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. wangtengfei2024@163.com.
Qinghua QiuDepartment of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. qinghuaqiu@163.com.

Funding

Joint Funds for the Innovation of Science and Technology, Fujian Province 2024Y9021National Outstanding Youth Science Fund Project of National Natural Science Foundation of China 82371072
6 · The paper itself

Abstract

backgroundThis study aims to elucidate the effect and mechanism of phospholipid transfer protein (PLTP) on vascular dysfunction in DR and explore the molecular mechanism of abnormal PLTP expression based on DNA methylation.

methodsHuman retinal microvascular endothelial cells (HRMECs) cultured in high glucose (HG) and streptozotocin-treated mice were used as DR models to detect and screen the key genes with abnormal promoter DNA methylation. Single-cell sequencing, tube formation and migration assays were employed to verify the relationship between PLTP and vascular function. Additionally, siRNA and luciferase reporter assay were used to study the key enzymes regulating the DNA methylation of PLTP. Transcriptome sequencing, coimmunoprecipitation and GSK3β inhibitor were utilized to identify and validate the key downstream pathways of PLTP.

resultsDR models exhibited DNA hypermethylation and decreased expression of PLTP. Abnormal PLTP expression was implicated in vascular dysfunction, and PLTP overexpression reversed HG-induced effects on the migration and tube formation of endothelial cells. The siDNMT3B and luciferase reporter assay indicated that DNMT3B is the primary enzyme affecting abnormal methylation. Interestingly, PLTP promoted the phosphorylation of AKT and GSK3β, indicating that PLTP modulates angiogenesis via the AKT/GSK3β signaling pathway.

conclusionsPLTP regulates the proliferation, migration and tube formation of HRMECs, and is involved in maintaining vascular function via the AKT/GSK3β signaling pathway. In HG environment, increased DNMT3B expression upregulates DNA methylation of the PLTP promoter, downregulating PLTP expression and leading to vascular dysfunction in DR.

Indexed as

Diabetic RetinopathyDNA (Cytosine-5-)-MethyltransferasesDNA MethylationGlycogen Synthase Kinase 3 betaPhospholipid Transfer ProteinsAnimalsCell MovementDiabetes Mellitus, ExperimentalDNA Methyltransferase 3BEndothelial CellsHumansMaleMiceMice, Inbred C57BLPromoter Regions, GeneticProto-Oncogene Proteins c-aktDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BGlycogen Synthase Kinase 3 betaPhospholipid Transfer ProteinsProto-Oncogene Proteins c-aktDiabetic retinopathy (DR)DNA methylationEpigeneticsPhospholipid transfer protein (PLTP)Vascular dysfunction

Identifiers

PMID40380281
PMCPMC12085079

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.