Evidence mapPaperPMID 40520008Full record

ArticleInternational journal of biological sciences2025

METTL3 mediated m6A modification of HKDC1 promotes renal injury and inflammation in lead nephropathy.

Xiao-Guo Suo, Jia-Nan Wang, Qi Zhu, Meng-Meng Zhang, Qing-Lin Ge, Li-Jin Peng, Yue-Yue Wang, Ming-Lu Ji, Yang-Mei Ou, Ju-Tao Yu and 13 more

Abstract read
In one paragraph

Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. The Role of NMedComm · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. Review
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

23 authors.

Xiao-Guo SuoInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Jia-Nan WangInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Qi ZhuInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Meng-Meng ZhangInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Qing-Lin GeInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Li-Jin PengInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Yue-Yue WangInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Ming-Lu JiInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Yang-Mei OuInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Ju-Tao YuInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Hao LuInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Xin-Ran ChengInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Bing-Bing HouDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
Xin ChenInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Sai ZhuInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Xiang-Yu LiInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Chao LiInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Shuai-Shuai XieInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Chen YangInstitute of Nephrology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Road, Zhanjiang 524001, China.
Feng-He LiInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Juan JinInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Fang WangInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Xiao-Ming MengInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Environmental and industrial Pb exposure poses a significant public health challenge. Acute exposure to high Pb concentrations can result in renal injury. Here, we revealed that N6-methyladenosine (m6A) RNA methylation was significantly upregulated in lead nephropathy and was mainly mediated by the methyltransferase METTL3. Functionally, METTL3 knockout in renal tubular epithelial cells or AAV9-mediated METTL3 silencing alleviated renal injury and the inflammatory response induced by lead acetate. METTL3 silencing in renal tubular epithelial cells reduced both m6A RNA methylation and inflammatory responses following lead acetate treatment. We identified hexokinase domain-containing 1 (HKDC1), known to function in the glycolytic pathway, as a direct METTL3 target. Importantly, HKDC1 was upregulated at both mRNA and protein levels after lead acetate treatment, thereby promoting renal injury and inflammation. Mechanistically, HKDC1 binds to ATPB and antagonizes the ubiquitinase Murf1, thereby leading to increased expression of ATPB and activation of the NF-κB signaling pathway, which promotes renal inflammation. We further confirmed that STM2457, an inhibitor of METTL3, protected against renal injury and inflammation induced by lead acetate. Collectively, our study demonstrated that the METTL3/HKDC1 axis is a potential target for the treatment of lead nephropathy, and STM2457 is expected to be a protective agent against renal injury caused by lead acetate.

Indexed as

AdenosineHexokinaseInflammationKidney DiseasesMethyltransferasesAnimalsHumansMaleMethylationMiceOrganometallic CompoundsSignal TransductionAdenosineHexokinaselead acetateMethyltransferasesMETTL3 protein, humanMettl3 protein, mouseN-methyladenosineOrganometallic CompoundsHKDC1Lead nephropathyMETTL3Renal inflammation

Identifiers

PMID40520008
PMCPMC12160926

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.