Evidence map›Paper›PMID 27129272›Full record

ArticleThe Journal of biological chemistry2016

Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.

Toshimi Tando, Akiyoshi Hirayama, Mitsuru Furukawa, Yuiko Sato, Tami Kobayashi, Atsushi Funayama, Arihiko Kanaji, Wu Hao, Ryuichi Watanabe, Mayu Morita and 10 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 58 citations in OpenAlex.

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  12. The mechanosensitive geneAmerican journal of physiology. Cell physiology · 2024
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  14. Association of a variant upstream ofTranslational animal science · 2023
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  20. Review
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

20 authors at 2 institutions in 1 country.

Toshimi TandoFrom the Departments of Orthopedic Surgery.
Akiyoshi Hirayamathe Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, and.
Mitsuru FurukawaFrom the Departments of Orthopedic Surgery.
Yuiko SatoFrom the Departments of Orthopedic Surgery, Musculoskeletal Reconstruction and Regeneration Surgery.
Tami KobayashiFrom the Departments of Orthopedic Surgery, Musculoskeletal Reconstruction and Regeneration Surgery.
Atsushi FunayamaFrom the Departments of Orthopedic Surgery.
Arihiko KanajiFrom the Departments of Orthopedic Surgery.
Wu HaoFrom the Departments of Orthopedic Surgery.
Ryuichi WatanabeFrom the Departments of Orthopedic Surgery.
Mayu MoritaDentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582.
Takatsugu OikeFrom the Departments of Orthopedic Surgery.
Kana MiyamotoFrom the Departments of Orthopedic Surgery.
Tomoyoshi Sogathe Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, and.
Masatoshi Nomurathe Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi Ward, Fukuoka 812-8582, Japan.
Akihiko YoshimuraImmunology, and.
Masaru Tomitathe Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, and.
Morio MatsumotoFrom the Departments of Orthopedic Surgery.
Masaya NakamuraFrom the Departments of Orthopedic Surgery.
Yoshiaki ToyamaFrom the Departments of Orthopedic Surgery.
Takeshi MiyamotoFrom the Departments of Orthopedic Surgery, miyamoto@z5.keio.jp.
Keio University · JPKyushu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.

Indexed as

Amino Acids, Branched-ChainAnimalsBlotting, WesternCell LineGlucoseInsulin-Like Growth Factor IMice, KnockoutMice, TransgenicMuscle DenervationMuscle Fibers, SkeletalMuscle ProteinsMuscle, SkeletalMuscular AtrophyMyostatinReceptor, IGF Type 1Restraint, PhysicalAmino Acids, Branched-ChainFbxo32 protein, mouseGlucoseInsulin-Like Growth Factor IMuscle ProteinsMyostatinReceptor, IGF Type 1SKP Cullin F-Box Protein LigasesSmad2 ProteinSmad3 ProteinTrim63 protein, mouseTripartite Motif ProteinsUbiquitin-Protein Ligasesmetabolismmusclemuscle atrophymyostatinSMAD transcription factor

Identifiers

PMID27129272
PMCPMC4933268
OpenAlexW2418204834

What OpenQuestion holds

Textmetadata
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.