Evidence mapPaperPMID 40100069Full record

ArticleJournal of cellular and molecular medicine2025

Inhibition of METTL3 Attenuates Renal Fibrosis by Upregulating ABCG2 m6A Modifications via IGF2BP2-Dependent Mechanisms in Hyperuricemic Nephropathy.

Tong Zu, Hang Yang, Jie Wang, Shuangjian Li, Yue Yu, Kuo Zhang, Xiuxiu Song, Jie Ying, Yaru Yang, Xian Wang and 1 more

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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

11 authors.

Tong ZuSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Hang YangSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Jie WangSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Shuangjian LiInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.
Yue YuSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Kuo ZhangSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Xiuxiu SongSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Jie YingSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.
Yaru YangInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.
Xian WangDepartment of Nephrology, Fuyang People's Hospital of Anhui Medical University, Fuyang, Anhui, China.
Juan JinSchool of Basic Medicine, School of Pharmacy, Anhui Medical University, Hefei, China.ORCID 0000-0003-3087-1555

Funding

National Natural Science Foundation of China 82100727
6 · The paper itself

Abstract

Hyperuricemia has been linked to kidney problems including hyperuricemic nephropathy (HN), which is characterised by inflammation and fibrosis in the kidneys. HN is frequently observed in patients with chronic gout. However, the causes of HN are not fully understood and effective treatments are limited. The status of RNA m6A, expression, and location of METTL3 in the kidney was evaluated in mice with HN. The mechanism of the METTL3-associated ABCG2 downregulation was further studied in mTEC cells and a potassium oxazinate + adenine-induced mice model and adeno-associated virus 9 (AAV9)-mediated METTL3 silencing mice. Expressions of ABCG2, α-SMA, collagen-1, TGF-β1, IL-1β, IL-6, and TNF-α were analysed using real-time PCR and western blotting. Hyperuricemia led to elevated m6A levels and METTL3 expression in mouse kidneys. METTL3 was mainly located in mTEC cells. METTL3-specific inhibitor STM2457 alleviated uric acid-induced inflammatory and fibrotic responses in mTEC cells. Mechanistically, ABCG2 was identified as a target of METTL3 by RNA sequencing. The stability of ABCG2 was decreased through the binding of IGF2BP2 (insulin-like growth factor 2 binding protein 2) to its m6A-modified stop codon regions. Silencing or inhibition of METTL3 significantly reduced uric acid-induced cell injury and increased ABCG2 expression, leading to uric acid excretion. In vivo data showed that AAV9-mediated METTL3 silencing significantly alleviated renal dysfunction and fibrosis in HN mice. Our study provides the first evidence that METTL3 regulates uric acid excretion by controlling the m6A levels of ABCG2 through the binding of IGF2BP2, and inhibiting METTL3 can effectively alleviate kidney damage caused by hyperuricemia, showing potential as a therapy for HN.

Indexed as

AdenosineATP Binding Cassette Transporter, Subfamily G, Member 2HyperuricemiaKidney DiseasesMethyltransferasesNeoplasm ProteinsRNA-Binding ProteinsAnimalsDisease Models, AnimalFibrosisHumansKidneyMaleMiceMice, Inbred C57BLUp-RegulationAbcg2 protein, mouseAdenosineATP Binding Cassette Transporter, Subfamily G, Member 2MethyltransferasesMettl3 protein, mouseNeoplasm ProteinsRNA-Binding ProteinsABCG2hyperuricemiaIGF2BP2METTL3mRNA m6A

Identifiers

PMID40100069
PMCPMC11916250

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.