Evidence map›Paper›PMID 28637784›Full record

ArticleCirculation research2017

TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3- and NF-kB-Dependent Activation of OPA1 Expression.

Jinliang Nan, Hengxun Hu, Yong Sun, Lianlian Zhu, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Na Zhang, Ya Wang, Yaping Wang and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

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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

15 authors at 2 institutions in 1 country.

Jinliang NanFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Hengxun HuFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yong SunFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Lianlian ZhuFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yingchao WangFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhiwei ZhongFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jing ZhaoFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Na ZhangFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ya WangFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yaping WangFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jian YeFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ling ZhangFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xinyang HuFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Wei ZhuFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jian'an WangFrom the Cardiovascular Key Laboratory of Zhejiang Province, Department of Cardiology (J.N., H.H., Y.S., L.Z., Y.W., Z.Z., J.Z., N.Z., Y.W., Y.W., J.Y., L.Z., X.H., W.Z., J.W.) and Clinical Research Center (L.Z., Y.W., Z.Z., J.Z.), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. jian_an_wang@yahoo.com weizhu65@zju.edu.cn.
ZTE (United States) · USHi-Z Technology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleMitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having proinflammatory and proapoptotic effects, TNFα (tumor necrosis factor α) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFR2 (TNFα receptor 2).

objectiveThe present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria. METHODS AND

resultsFreshly isolated neonatal mouse cardiac myocytes treated with shRNA targeting TNFR1 were used to study the effects of TNFR2 activation on mitochondrial function. Neonatal mouse cardiac myocytes exhibited increases in mitochondrial fusion, a change that was associated with increases in mitochondrial membrane potential, intracellular ATP levels, and oxygen consumption capacity. Importantly, TNFR2 activation-induced increases in OPA1 (optic atrophy 1) protein expression were responsible for the above enhancements, and these changes could be attenuated using siRNA targeting OPA1. Moreover, both Stat3 and RelA bound to the promoter region of OPA1 and their interactions synergistically upregulated OPA1 expression at the transcriptional level. Stat3 acetylation at lysine 370 or lysine 383 played a key role in the ability of Stat3 to form a supercomplex with RelA. Meanwhile, p300 modulated Stat3 acetylation in HEK293T (human embryonic kidney 293T) cells, and p300-mediated Stat3/RelA interactions played an indispensable role in OPA1 upregulation. Finally, TNFR2 activation exerted beneficial effects on OPA1 expression in an in vivo transverse aortic constriction model, whereby TNFR1-knockout mice exhibited better outcomes than in mice with both TNFR1 and TNFR2 knocked out.

conclusionsTNFR2 activation protects cardiac myocytes against stress by upregulating OPA1 expression. This process was facilitated by p300-mediated Stat3 acetylation and Stat3/RelA interactions, leading to improvements in mitochondrial morphology and function.

Indexed as

AnimalsAnimals, NewbornAortic DiseasesCells, CulturedGene ExpressionGTP PhosphohydrolasesHEK293 CellsHumansMiceMice, Inbred C57BLMice, KnockoutMitochondrial DynamicsMyocytes, CardiacNF-kappa BProtein Structure, SecondaryProtein Structure, TertiaryGTP PhosphohydrolasesNF-kappa BOpa1 protein, mouseReceptors, Tumor Necrosis Factor, Type IIStat3 protein, mouseSTAT3 Transcription Factoracetylationheart failuremitochondrial dynamicsmolecular dynamics simulationtumor necrosis factor-alpha

Identifiers

PMID28637784
PMCPMC5542782
OpenAlexW2687790521

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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.