Evidence map›Paper›PMID 39294131›Full record

ArticleCell death & disease2024

The functional role of m6A demethylase ALKBH5 in cardiomyocyte hypertrophy.

Chen Meng, Haibi Su, Meiling Shu, Feng Shen, Yijie Lu, Shishi Wu, Zhenghua Su, Mengyao Yu, Di Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. mExperimental & molecular medicine · 2025
    Review
  7. Methylations in dilated cardiomyopathy and heart failure.Frontiers in cardiovascular medicine · 2025
    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

9 authors.

Chen MengHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China.
Haibi SuHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China.
Meiling ShuHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China.
Feng ShenDepartment of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China.
Yijie LuHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China.
Shishi WuHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China.
Zhenghua SuHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China.
Mengyao YuHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China. yumengyao@fudan.edu.cn.
Di YangHuman Phenome Institute, Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Zhangjiang Fudan International Innovation Center, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, China. diyang@fudan.edu.cn.ORCID 0000-0002-4768-2286

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81903602Shanghai Municipal Health Bureau (Shanghai Municipal Public Health Bureau) 20234Y0238
6 · The paper itself

Abstract

Cardiomyocyte hypertrophy is a major outcome of pathological cardiac hypertrophy. The m6A demethylase ALKBH5 is reported to be associated with cardiovascular diseases, whereas the functional role of ALKBH5 in cardiomyocyte hypertrophy remains confused. We engineered Alkbh5 siRNA (siAlkbh5) and Alkbh5 overexpressing plasmid (Alkbh5 OE) to transfect cardiomyocytes. Subsequently, RNA immunoprecipitation (RIP)-qPCR, MeRIP-qPCR analysis and the dual-luciferase reporter assays were applied to elucidate the regulatory mechanism of ALKBH5 on cardiomyocyte hypertrophy. Our study identified ALKBH5 as a new contributor of cardiomyocyte hypertrophy. ALKBH5 showed upregulation in both phenylephrine (PE)-induced cardiomyocyte hypertrophic responses in vitro and transverse aortic constriction (TAC)/high fat diet (HFD)-induced pathological cardiac hypertrophy in vivo. Knockdown or overexpression of ALKBH5 regulated the occurrence of hypertrophic responses, including the increased cardiomyocyte surface areas and elevation of the hypertrophic marker levels, such as brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Mechanically, we indicated that ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth. Our work highlights the functional role of ALKBH5 in regulating the onset of cardiomyocyte hypertrophy and provides a potential target for hypertrophic heart diseases prevention and treatment. ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth.

Indexed as

AlkB Homolog 5, RNA DemethylaseCardiomegalyJanus Kinase 2Myocytes, CardiacSTAT3 Transcription FactorAdenosineAnimalsHumansMaleMiceMice, Inbred C57BLNatriuretic Peptide, BrainPhenylephrineRatsRats, Sprague-DawleySignal TransductionAdenosineALKBH5 protein, mouseAlkB Homolog 5, RNA DemethylaseJanus Kinase 2Natriuretic Peptide, BrainN-methyladenosinePhenylephrineSTAT3 Transcription Factor

Identifiers

PMID39294131
PMCPMC11410975

What OpenQuestion 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 OpenQuestion graph.