Evidence map›Paper›PMID 42834249›Full record

ArticleMolecular biomedicine2026

Lactate-induced MBD2 K186 lactylation promotes YAP1-dependent myofibroblast-like remodeling of Müller cells in diabetic retinopathy.

Xindan Xing, Yan Jiang, Junwei Fang, Xin Shi, Qian Zhu, Yinchen Shen, Li Su, Xinyi Liu, Hanying Wang, Jin Wei and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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

18 authors.

Xindan Xing *Department of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Yan Jiang *Department of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Junwei Fang *Department of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Xin ShiDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Qian ZhuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Yinchen ShenDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Li SuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Xinyi LiuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Hanying WangDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Jin WeiDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Yuan QuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Kangjia LvDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Yu XiaoDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Jingtong XieDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Xiaoxin LiuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Hancong WanDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.
Tian NiuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China. niutian_up@163.com.ORCID http://orcid.org/0000-0002-0377-3151
Kun LiuDepartment of Ophtalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China. drliukun@sjtu.edu.cn.ORCID http://orcid.org/0000-0002-0115-7160

Funding

Basic and Clinical Collaborative Research Program of Shanghai General Hospital JC202622Characteristic Shanghai leading talents training Program 02.06.01.21.06Fundamental Research Funds for the Central Universities YG2025ZD26Innovative Pharmaceutical and Medical Device Products Application Project of Shanghai Science and Technology Commission 24SF1905600National Clinical Key Specialty Construction Project 10000015Z155080000004National Natural Science Foundation of China 82201211National Natural Science Foundation of China 82471109Natural Science Foundation of Shanghai 24ZR1458600
6 · The paper itself

Abstract

Tractional retinal detachment caused by fibroproliferative membrane formation is a vision-threatening complication of proliferative diabetic retinopathy (PDR). Müller cells can acquire myofibroblast-like features during retinal fibroproliferative remodeling, yet the metabolic mechanisms governing these phenotypic changes remain poorly understood. Here, we report that lactate is a metabolic regulator of myofibroblast-like remodeling in Müller cells. Metabolomic profiling revealed elevated vitreous lactate levels in patients with PDR. Consistently, lactate concentrations were increased in the vitreous and retinal tissues of diabetic rats, whereas high-glucose exposure promoted lactate accumulation in primary Müller cells. Increased lactate availability enhanced Müller cell proliferative activity and migration, as well as the expression of myofibroblast-associated proteins, including α-smooth muscle actin, smooth muscle protein 22, and collagen I, whereas oxamate, an inhibitor of lactate dehydrogenase, attenuated these responses. Lactylome profiling and molecular validation revealed K186 of methyl-CpG-binding domain protein 2 (MBD2) as a functionally relevant lactylation site. RNA sequencing of high-glucose-treated Müller cells expressing MBD2-K186R versus MBD2-WT revealed reduced YAP1 expression in the K186R group, suggesting that YAP1 is a downstream effector of MBD2 K186 lactylation. Mechanistically, increased lactate availability enhanced MBD2 K186 lactylation and YAP1 activation, as evidenced by reduced inhibitory phosphorylation of YAP1 and increased nuclear accumulation of YAP1. MBD2 K186R attenuated YAP1 activation and myofibroblast-like changes, whereas YAP1 overexpression partially reversed these effects. Collectively, these findings reveal a lactate-MBD2 K186 lactylation-YAP1 signaling axis that promotes myofibroblast-like remodeling of Müller cells and may contribute to fibroproliferative pathology in PDR.

Indexed as

Adaptor Proteins, Signal TransducingDiabetic RetinopathyDNA-Binding ProteinsEpendymoglial CellsLactic AcidMyofibroblastsTranscription FactorsAnimalsCell ProliferationHumansMaleRatsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingDNA-Binding ProteinsLactic AcidTranscription FactorsYap1 protein, ratYAP-Signaling ProteinsLactateMBD2–YAP1 signalingMüller cellsMyofibroblast-like phenotypeProliferative diabetic retinopathyProtein lactylation

Identifiers

PMID42834249
PMCPMC13638938

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.