Evidence map›Paper›PMID 41094513›Full record

ArticleJournal of translational medicine2025

Lactylation-induced ALKBH5 targets RNF123 to worsen retinal Müller cell activation through PKM2-regulated Glycolysis in diabetic retinopathy.

Shasha Luo, Ye Sun, Yifan Hu, Yujia Xu

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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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

4 authors.

Shasha LuoDepartment of Ophthalmology, Wuxi No. 2 People's Hospital (Jiangnan University Medical Center), Wuxi, 214000, China. luoshasha403@163.com.
Ye SunDepartment of Ophthalmology, Jiangnan University Wuxi School of Medicine, Wuxi, 214000, China.
Yifan HuDepartment of Ophthalmology, Jiangnan University Wuxi School of Medicine, Wuxi, 214000, China.
Yujia XuDepartment of Ophthalmology, Jiangnan University Wuxi School of Medicine, Wuxi, 214000, China.

Funding

"Taihu Talents" Science and Technology Research (Basic Research) Project of the Wuxi Science and Technology Bureau in 2022 K20221031the Top Talent Support Program for the young and middle-aged people of Wuxi Health Committee in 2023 BJ2023038
6 · The paper itself

Abstract

backgroundUbiquitin ligase RNF123 affects a variety of pathological processes, but little is known about its regulatory mechanism. This study defined the regulatory mechanisms of RNF123 in Müller cell activation in diabetic retinopathy (DR).

methodsRNF123 expression was analyzed in the retina of DR patients and diabetic mice. Müller cell line MIO-M1 treated with high glucose (HG) was used to explore the upstream and downstream signal regulation mechanism of RNF123 in vitro. Müller cell activation and glycolysis were indicated using cell viability, cell migration, levels of inflammatory factors, GFAP and GS expression levels, extracellular acidification rate and lactate production. Diabetic rat models induced by streptozotocin were used to investigate the critical role of the RNF123-glycolytic axis in DR in vivo.

resultsRNF123 expression was decreased in the retina of DR patients, diabetic mice and HG-stimulated Müller cells. HG-induced pathological activation of MIO-M1 cells, manifested as increased viability, migration, inflammatory factors production and GFAP expression and decreased GS expression, and also increased glycolysis. These pathological changes were reversed by RNF123 overexpression. Glycolysis inhibition by 2-DG reversed RNF123 knockdown-induced Müller cell activation. RNF123 targeting ubiquitination of PKM2 in HG-induced MIO-M1 cell activation. HG-induced downregulation of RNF123 was regulated by ALKBH5 and IGF2BP1-mediated m6A modification. HG-induced upregulation of ALKBH5 was mediated by histone lactylation. The lactate-ALKBH5-RNF123-PKM2 regulatory axis was involved in HG-induced Müller cell activation and retinal damage of the diabetic rats.

conclusionsLactate increases glycolysis through the ALKBH5-RNF123-PKM2 signaling axis to form a feedback regulation mechanism to activate Müller cells, which is an important pathological mechanism of DR.

Indexed as

Carrier ProteinsDiabetic RetinopathyEpendymoglial CellsGlycolysisMembrane ProteinsThyroid HormonesUbiquitin-Protein LigasesAnimalsCell LineCell MovementDiabetes Mellitus, ExperimentalGlucoseHumansMaleMiceMice, Inbred C57BLCarrier ProteinsGlucoseMembrane ProteinsPkm protein, mousePyruvate KinaseThyroid Hormone-Binding ProteinsThyroid HormonesUbiquitin-Protein LigasesDiabetic retinopathyGlycolysisHistone lactylationMüller cellsN6-MethyladenosineRNF123Ubiquitination

Identifiers

PMID41094513
PMCPMC12523176

What Socratic holds

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Registered trials

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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 Socratic graph.