Evidence mapPaperPMID 40421968Full record

ArticleJournal of cellular and molecular medicine2025

The Impact of METTL3 on MDM2 Promotes Podocytes Injury During Diabetic Kidney Disease.

Han Wu, Ziyang Yu, Yitian Yang, Zhuoting Han, Qingjun Pan, Ying Chen, Hongyuan Yu, Siman Shen, Li Xu

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
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

9 authors.

Han WuDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Ziyang YuSchool of Medicine Xiamen University, Xiamen, China.
Yitian YangRespiratory Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Zhuoting HanDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Qingjun PanClinical Research and Experimental Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.ORCID 0000-0002-8060-9099
Ying ChenDepartment of Nephrology, The First Hospital of China Medical University, Shenyang, China.
Hongyuan YuDepartment of Urology, The First Hospital of China Medical University, Shenyang, China.ORCID 0000-0003-2106-0304
Siman ShenDepartment of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Li XuDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.ORCID 0009-0000-2900-2040

Funding

China Postdoctoral Science Foundation 2021M703608Guangdong Medical University Clinical and Basic Science Innovation Special Project GDMULCJC2024053Guangdong Natural Science Foundation-General Program 2025A1515010621The National Natural Science Foundation of China 81800642Zhanjiang Science and Technology Development Special Project 2022A01110Zhanjiang Science and Technology Development Special Project 2022A01142
6 · The paper itself

Abstract

N6-Methyladenosine (m6A) methylation plays a role in various pathological processes, including renal fibrosis and aging. Our previous studies have highlighted abnormal expression of the methyltransferase enzyme, methyltransferase like 3 (METTL3), in aging kidney tissues. This study aims to elucidate the regulatory mechanisms of METTL3 in diabetic kidney disease (DKD) by establishing a conditional METTL3 knockout model. We observed elevated m6A levels in the kidneys of type I diabetic mice and in cultured mouse podocytes exposed to advanced glycation end products (AGEs). These increases were attributed to enhanced METTL3 expression. Significantly, podocyte-specific METTL3 knockdown mitigated injury in streptozotocin (STZ)-induced diabetic mice, evidenced by reduced urine albuminuria and renal pathology. We discovered that METTL3 induced abnormal m6A modification of murine double minute 2 (MDM2), which triggered its degradation in an IGF2BP2 (insulin-like growth factor 2 mRNA-binding protein 2)-dependent manner. This modification led to increased MDM2 expression, activating the Notch signalling pathway and inducing podocyte cell cycle arrest under diabetic conditions, which further released inflammatory factors and caused podocyte dedifferentiation. Our findings suggest that targeting m6A modification via METTL3 could be an effective strategy for treating DKD.

Indexed as

Diabetic NephropathiesMethyltransferasesPodocytesProto-Oncogene Proteins c-mdm2AdenosineAnimalsDiabetes Mellitus, ExperimentalGlycation End Products, AdvancedMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionAdenosineGlycation End Products, AdvancedMdm2 protein, mouseMethyltransferasesMettl3 protein, mouseN-methyladenosineProto-Oncogene Proteins c-mdm2dedifferentiationdiabetic kidney diseasemurine double minute 2N6‐Methyladenosinepodocytes

Identifiers

PMID40421968
PMCPMC12107706

What Socratic holds

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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 Socratic graph.