Evidence map›Paper›PMID 29040534›Full record

ArticleHuman molecular genetics2018

Macrophages escape Klotho gene silencing in the mdx mouse model of Duchenne muscular dystrophy and promote muscle growth and increase satellite cell numbers through a Klotho-mediated pathway.

Michelle Wehling-Henricks, Steven S Welc, Guiseppina Samengo, Chiara Rinaldi, Catherine Lindsey, Ying Wang, Jeongyoon Lee, Makoto Kuro-O, James G Tidball

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

Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 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

9 authors at 2 institutions in 2 countries.

Michelle Wehling-HenricksDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
Steven S WelcDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
Guiseppina SamengoDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
Chiara RinaldiDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
Catherine LindseyDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
Ying WangMolecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, CA 90095, USA.
Jeongyoon LeeDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
Makoto Kuro-ODivision of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Yakushiji, Shimotsuke, Tochigi, Japan.
James G TidballDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
University of California, Los Angeles · USJichi Medical University · JP

Funding

Myeloid-cell mediated mechanisms driving muscle growth and regenerationR01AR066036 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2014 to 2018
$1.8M
Immune cell regulation of the regeneration of dystrophic muscleR01AR062579 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2014 to 2018
$1.7M
Functions of myelomonocytic lineage cells in aging muscleR01AG041147 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2011 to 2015
$1.7M
Targeting Therapeutic Molecules to Dystrophic Muscle via the Immune SystemR21AR066817 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIDBALL, JAMES G · 2014 to 2015
$373k
NIAMS NIH HHS R01 AR062579NIAMS NIH HHS R01 AR066036NIAMS NIH HHS R21 AR066817NIA NIH HHS R01 AG041147
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is a muscle wasting disease in which inflammation influences the severity of pathology. We found that the onset of muscle inflammation in the mdx mouse model of DMD coincides with large increases in expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNFα); interferon gamma (IFNγ)] and dramatic reductions of the pro-myogenic protein Klotho in muscle cells and large increases of Klotho in pro-regenerative, CD206+ macrophages. Furthermore, TNFα and IFNγ treatments reduced Klotho in muscle cells and increased Klotho in macrophages. Because CD206+/Klotho+ macrophages were concentrated at sites of muscle regeneration, we tested whether macrophage-derived Klotho promotes myogenesis. Klotho transgenic macrophages had a pro-proliferative influence on muscle cells that was ablated by neutralizing antibodies to Klotho and conditioned media from Klotho mutant macrophages did not increase muscle cell proliferation in vitro. In addition, transplantation of bone marrow cells from Klotho transgenic mice into mdx recipients increased numbers of myogenic cells and increased the size of muscle fibers. Klotho also acted directly on macrophages, stimulating their secretion of TNFα. Because TNFα is a muscle mitogen, we tested whether the pro-proliferative effects of Klotho on muscle cells were mediated by TNFα and found that increased proliferation caused by Klotho was reduced by anti-TNFα. Collectively, these data show that pro-inflammatory cytokines contribute to silencing of Klotho in dystrophic muscle, but increase Klotho expression by macrophages. Our findings also show that macrophage-derived Klotho can promote muscle regeneration by expanding populations of muscle stem cells and increasing muscle fiber growth in dystrophic muscle.

Indexed as

AnimalsCytokinesDisease Models, AnimalGene SilencingGlucuronidaseHumansInflammationKlotho ProteinsMacrophagesMiceMice, Inbred mdxMuscle, SkeletalMuscular Dystrophy, AnimalMuscular Dystrophy, DuchenneMyoblastsCytokinesGlucuronidaseKlotho Proteins

Identifiers

PMID29040534
PMCPMC5886268
OpenAlexW2761764474

What OpenQuestion holds

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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.