Evidence map›Paper›PMID 26972746›Full record

ArticleScientific reports2016

Using AAV vectors expressing the β2-adrenoceptor or associated Gα proteins to modulate skeletal muscle mass and muscle fibre size.

Adam Hagg, Timothy D Colgan, Rachel E Thomson, Hongwei Qian, Gordon S Lynch, Paul Gregorevic

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Influence of βRespiratory research · 2019
    Article
  7. Review
  8. Protein kinase A activation inhibitsThe Journal of biological chemistry · 2018
    Article
  9. Article
  10. Article
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 2 countries.

Adam HaggBaker IDI Heart and Diabetes Institute, Melbourne, 3004, Australia.
Timothy D ColganBaker IDI Heart and Diabetes Institute, Melbourne, 3004, Australia.
Rachel E ThomsonBaker IDI Heart and Diabetes Institute, Melbourne, 3004, Australia.
Hongwei QianBaker IDI Heart and Diabetes Institute, Melbourne, 3004, Australia.
Gordon S LynchDept. of Physiology, The University of Melbourne, Melbourne, 3010, Australia.
Paul GregorevicBaker IDI Heart and Diabetes Institute, Melbourne, 3004, Australia.
Baker Heart and Diabetes Institute · AUUniversity of Melbourne · AUUniversity of Washington · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anabolic β2-adrenoceptor (β2-AR) agonists have been proposed as therapeutics for treating muscle wasting but concerns regarding possible off-target effects have hampered their use. We investigated whether β2-AR-mediated signalling could be modulated in skeletal muscle via gene delivery to the target tissue, thereby avoiding the risks of β2-AR agonists. In mice, intramuscular administration of a recombinant adeno-associated virus-based vector (rAAV vector) expressing the β2-AR increased muscle mass by >20% within 4 weeks. This hypertrophic response was comparable to that of 4 weeks' treatment with the β2-AR agonist formoterol, and was not ablated by mTOR inhibition. Increasing expression of inhibitory (Gαi2) and stimulatory (GαsL) G-protein subunits produced minor atrophic and hypertrophic changes in muscle mass, respectively. Furthermore, Gαi2 over-expression prevented AAV:β2-AR mediated hypertrophy. Introduction of the non-muscle Gαs isoform, GαsXL elicited hypertrophy comparable to that achieved by AAV:β2-AR. Moreover, GαsXL gene delivery was found to be capable of inducing hypertrophy in the muscles of mice lacking functional β1- and β2-ARs. These findings demonstrate that gene therapy-based interventions targeting the β2-AR pathway can promote skeletal muscle hypertrophy independent of ligand administration, and highlight novel methods for potentially modulating muscle mass in settings of disease.

Indexed as

Adrenergic beta-2 Receptor AgonistsAnimalsBlotting, WesternDependovirusFormoterol FumarateGenetic VectorsGene Transfer TechniquesGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, GsHypertrophyMaleMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescenceMuscle Fibers, SkeletalMuscle, SkeletalAdrenergic beta-2 Receptor AgonistsFormoterol FumarateGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, GsMyosin Type IIReceptors, Adrenergic, beta-2

Identifiers

PMID26972746
PMCPMC4789796
OpenAlexW2411836117

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Registered trials

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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.