Evidence map›Paper›PMID 33045622›Full record

ArticleRedox biology2020

Meteorin-like protein attenuates doxorubicin-induced cardiotoxicity via activating cAMP/PKA/SIRT1 pathway.

Can Hu, Xin Zhang, Peng Song, Yu-Pei Yuan, Chun-Yan Kong, Hai-Ming Wu, Si-Chi Xu, Zhen-Guo Ma, Qi-Zhu Tang

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed
18.9field-weighted citation impact, top 1% of its field
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

122 citing papers in PubMed, 236 citations in OpenAlex.

  1. Article
  2. Metrnl in mitigating radiation enteritisActa pharmaceutica Sinica. B · 2026
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  12. Metrnl in health and disease: tissue-specific actions and signaling networks.Apoptosis : an international journal on programmed cell death · 2026
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62 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Can HuDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Xin ZhangDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Peng SongDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Yu-Pei YuanDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Chun-Yan KongDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Hai-Ming WuDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Si-Chi XuDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China.
Zhen-Guo MaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China. Electronic address: zhengma@whu.edu.cn.
Qi-Zhu TangDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China. Electronic address: qztang@whu.edu.cn.
Renmin Hospital of Wuhan University · CNWuhan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Meteorin-like (METRNL) protein is a newly identified myokine that functions to modulate energy expenditure and inflammation in adipose tissue. Herein, we aim to investigate the potential role and molecular basis of METRNL in doxorubicin (DOX)-induced cardiotoxicity. METRNL was found to be abundantly expressed in cardiac muscle under physiological conditions that was decreased upon DOX exposure. Cardiac-specific overexpression of METRNL by adeno-associated virus serotype 9 markedly improved oxidative stress, apoptosis, cardiac dysfunction and survival status in DOX-treated mice. Conversely, knocking down endogenous METRNL by an intramyocardial injection of adenovirus exacerbated DOX-induced cardiotoxicity and death. Meanwhile, METRNL overexpression attenuated, while METRNL silence promoted oxidative damage and apoptosis in DOX-treated H9C2 cells. Systemic METRNL depletion by a neutralizing antibody aggravated DOX-related cardiac injury and dysfunction in vivo, which were notably alleviated by METRNL overexpression within the cardiomyocytes. Besides, we detected robust METRNL secretion from isolated rodent hearts and cardiomyocytes, but to a less extent in those with DOX treatment. And the beneficial effects of METRNL in H9C2 cells disappeared after the incubation with a METRNL neutralizing antibody. Mechanistically, METRNL activated SIRT1 via the cAMP/PKA pathway, and its antioxidant and antiapoptotic capacities were blocked by SIRT1 deficiency. More importantly, METRNL did not affect the tumor-killing action of DOX in 4T1 breast cancer cells and tumor-bearing mice. Collectively, cardiac-derived METRNL activates SIRT1 via cAMP/PKA signaling axis in an autocrine manner, which ultimately improves DOX-elicited oxidative stress, apoptosis and cardiac dysfunction. Targeting METRNL may provide a novel therapeutic strategy for the prevention of DOX-associated cardiotoxicity.

Indexed as

CardiotoxicitySirtuin 1AnimalsApoptosisDoxorubicinMiceMyocytes, CardiacOxidative StressDoxorubicinSirt1 protein, mouseSirtuin 1ApoptosisDoxorubicinMETRNLOxidative stressSIRT1

Identifiers

PMID33045622
PMCPMC7558217
OpenAlexW3092217910

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.