Evidence map›Paper›PMID 34812145›Full record

ArticleeLife2021

The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism.

Anirban Roy, Meiricris Tomaz da Silva, Raksha Bhat, Kyle R Bohnert, Takao Iwawaki, Ashok Kumar

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

22 citing papers in PubMed, 22 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

6 authors at 3 institutions in 3 countries.

Anirban RoyDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, United States.ORCID 0000-0002-5625-5403
Meiricris Tomaz da SilvaDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, United States.ORCID 0000-0002-7479-2595
Raksha BhatDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, United States.
Kyle R BohnertKinesiology Department, St Ambrose University, Davenport, United States.
Takao IwawakiDivision of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Japan.
Ashok KumarDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, United States.ORCID 0000-0001-8571-2848
Pharmac · NZKanazawa Medical University · JPSaint Ambrose University · US

Funding

TAK1/TRAF6 Signaling in Skeletal MuscleR01AR059810 · NIAMS · UNIVERSITY OF LOUISVILLE · PI KUMAR, ASHOK · 2011 to 2021
$4.0M
MYD88 Signaling in Mammalian Myoblast FusionR01AR068313 · NIAMS · UNIVERSITY OF LOUISVILLE · PI KUMAR, ASHOK · 2015 to 2019
$1.7M
NIAMS NIH HHS R01 AR059810NIAMS NIH HHS R01 AR068313
6 · The paper itself

Abstract

Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. However, the role of individual arms of the UPR in skeletal muscle regeneration remain less understood. In the present study, we demonstrate that IRE1α (also known as ERN1) and its downstream target, XBP1, are activated in skeletal muscle of mice upon injury. Myofiber-specific ablation of IRE1α or XBP1 in mice diminishes skeletal muscle regeneration that is accompanied with reduced number of satellite cells. Ex vivo cultures of myofiber explants demonstrate that ablation of IRE1α reduces the proliferative capacity of myofiber-associated satellite cells. Myofiber-specific ablation of IRE1α dampens Notch signaling and canonical NF-κB pathway in skeletal muscle of adult mice. Finally, targeted ablation of IRE1α also reduces Notch signaling, abundance of satellite cells, and skeletal muscle regeneration in the mdx mice, a model of Duchenne muscular dystrophy. Collectively, our experiments suggest that the IRE1α-mediated signaling promotes muscle regeneration through augmenting the proliferation of satellite cells in a cell non-autonomous manner.

Indexed as

AnimalsEndoribonucleasesMiceMice, Inbred mdxMice, KnockoutMuscle, SkeletalProtein Serine-Threonine KinasesRegenerationSignal TransductionUnfolded Protein ResponseX-Box Binding Protein 1EndoribonucleasesErn1 protein, mouseProtein Serine-Threonine KinasesX-Box Binding Protein 1Xbp1 protein, mousecell biologyER stressire1 signalingregenerationregenerative medicinesatellite cellsskeletal muscleskeletal muscle regenerationstem cellsXBP1

Identifiers

PMID34812145
PMCPMC8635982
OpenAlexW3216020325

What OpenQuestion holds

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LicenceCC BY
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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.