Evidence map›Paper›PMID 16967503›Full record

ArticleJournal of neurobiology2006

Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates neuromuscular junction development via a beta1 integrin-mediated mechanism.

Gentian Lluri, Garret D Langlois, Brian McClellan, Paul D Soloway, Diane M Jaworski

Open access · greenAbstract read
In one paragraph

Article in Journal of neurobiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

20 citing papers in PubMed, 36 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

5 authors at 2 institutions in 1 country.

Gentian LluriDepartment of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Garret D Langlois
Brian McClellan
Paul D Soloway
Diane M Jaworski
University of Vermont · USCornell University · US

Funding

VOLATILE SIGNALING IN PHARBITIS NILP20RR016462 · NCRR · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI KIRSHENBAUM, ARI PHILLIP · 2001 to 2011
$31.1M
Proteomics Core for Neuroscience P20 RR16435P20RR016435 · NCRR · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI SPEES, JEFFREY L · 2001 to 2010
$23.5M
TUMOR GROWTH AND METASTASISP30CA022435 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI FOGARTY, JOHN P · 1985 to 2007
$9.6M
Molecular Regulation of TIMP-2 in Neuron Cell CycleR01NS045225 · NINDS · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI JAWORSKI, DIANE M · 2004 to 2007
$1.4M
MOLECULAR REGULATION OF GLIAL MATRIX PROTEIN EXPRESSIONR29NS035874 · NINDS · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI JAWORSKI, DIANE M · 1997 to 2001
$297k
NCI NIH HHS P30 CA022435NCI NIH HHS P30CA22435NCRR NIH HHS 1P20 RR16435NCRR NIH HHS 1 P20 RR16462NCRR NIH HHS P20 RR016435NCRR NIH HHS P20 RR016462NINDS NIH HHS NS045225NINDS NIH HHS R01 NS045225NINDS NIH HHS R29 NS035874
6 · The paper itself

Abstract

Extracellular matrix (ECM) molecules play critical roles in muscle function by participating in neuromuscular junction (NMJ) development and the establishment of stable, cytoskeleton-associated adhesions required for muscle contraction. Matrix metalloproteinases (MMPs) are neutral endopeptidases that degrade all ECM components. While the role of MMPs and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs), has been investigated in many tissues, little is known about their role in muscle development and mature function. TIMP-2 -/- mice display signs of muscle weakness. Here, we report that TIMP-2 is expressed at the NMJ and its expression is greater in fast-twitch (extensor digitorum longus, EDL) than slow-twitch (soleus) muscle. EDL muscle mass is reduced in TIMP-2-/- mice without a concomitant change in fiber diameter or number. The TIMP-2-/- phenotype is not likely due to increased ECM proteolysis because net MMP activity is actually reduced in TIMP-2-/- muscle. Most strikingly, TIMP-2 colocalizes with beta1 integrin at costameres in the wild-type EDL and beta1 integrin expression is significantly reduced in TIMP-2-/- EDL. We propose that reduced beta1 integrin in fast-twitch muscle may be associated with destabilized ECM-cytoskeletal interactions required for muscle contraction in TIMP-2-/- muscle; thus, explaining the muscle weakness. Given that fast-twitch fibers are lost in muscular dystrophies and age-related sarcopenia, if TIMP-2 regulates mechanotransduction in an MMP-independent manner it opens new potential therapeutic avenues.

Indexed as

AnimalsCell DifferentiationCytoskeletonExtracellular MatrixIntegrin beta1Mechanotransduction, CellularMiceMice, KnockoutMuscle Fibers, Fast-TwitchMuscle Fibers, Slow-TwitchMuscle, SkeletalMuscle WeaknessMuscular DystrophiesNeuromuscular JunctionPhenotypeTissue Inhibitor of Metalloproteinase-2Integrin beta1Tissue Inhibitor of Metalloproteinase-2

Identifiers

PMID16967503
PMCPMC2982212
OpenAlexW2017637956

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.