Evidence map›Paper›PMID 34537816›Full record

ArticleCell death discovery2021

Trimetazidine attenuates dexamethasone-induced muscle atrophy via inhibiting NLRP3/GSDMD pathway-mediated pyroptosis.

Li Wang, Xin-Feng Jiao, Cheng Wu, Xiao-Qing Li, Hui-Xian Sun, Xi-Yu Shen, Kang-Zhen Zhang, Can Zhao, Li Liu, Man Wang and 6 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
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  5. Molecular medicine reports · 2026
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  12. Journal of microbiology and biotechnology · 2025
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3 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

16 authors at 2 institutions in 1 country.

Li Wang *Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Xin-Feng Jiao *Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Cheng WuKey Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, China.
Xiao-Qing LiKey Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, China.
Hui-Xian SunDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Xi-Yu ShenDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Kang-Zhen ZhangDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Can ZhaoDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Li LiuDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Man WangDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Yun-Ling BuDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Jia-Wen LiDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Fan XuDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Chen-Lu ChangDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Xiang LuDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China. luxiang66@njmu.edu.cn.ORCID http://orcid.org/0000-0001-8351-1778
Wei GaoDepartment of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China. gaowei84@njmu.edu.cn.ORCID http://orcid.org/0000-0002-4770-5062
Second Affiliated Hospital of Nanjing Medical University · CNNanjing Medical University · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81770440National Natural Science Foundation of China (National Science Foundation of China) 81970217National Natural Science Foundation of China (National Science Foundation of China) 81970218Six Talent Peaks Project in Jiangsu Province (Six Talent Peaks Project in Jiangsu Province of China) WSN-175
6 · The paper itself

Abstract

Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can improve skeletal muscle performance both in humans and mice. We here showed that dexamethasone-induced atrophy, as evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression, and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and gasdermin-D (GSDMD). Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine treatment ameliorated dexamethasone-induced muscle pyroptosis and atrophy both in vivo and in vitro. Activation of NLRP3 using LPS and ATP not only increased the cleavage and activation of Caspase-1 and GSDMD, but also increased the expression levels of atrophy markers MuRF1 and Atrogin-1 in trimetazidine-treated C2C12 myotubes. Mechanically, dexamethasone inhibited the phosphorylation of PI3K/AKT/FoxO3a, which could be attenuated by trimetazidine. Conversely, co-treatment with a PI3K/AKT inhibitor, picropodophyllin, remarkably increased the expression of NLRP3 and reversed the protective effects of trimetazidine against dexamethasone-induced C2C12 myotube pyroptosis and atrophy. Taken together, our study suggests that NLRP3/GSDMD-mediated pyroptosis might be a novel mechanism for dexamethasone-induced skeletal muscle atrophy. Trimetazidine might be developed as a potential therapeutic agent for the treatment of dexamethasone-induced muscle atrophy.

Identifiers

PMID34537816
PMCPMC8449784
OpenAlexW3200002328

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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.