Evidence map›Paper›PMID 33089917›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020

The role of neutrophil extracellular traps and TLR signaling in skeletal muscle ischemia reperfusion injury.

Nicole J Edwards, Charles Hwang, Simone Marini, Chase A Pagani, Philip J Spreadborough, Cassie J Rowe, Pauline Yu, Annie Mei, Noelle Visser, Shuli Li and 7 more

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

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.7field-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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  3. Targeting TGF-β to Attenuate Ischemia-Reperfusion Associated Muscle Fibrosis and Enhance Regeneration: A Preclinical Study.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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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

17 authors at 4 institutions in 1 country.

Nicole J EdwardsDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Charles HwangDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Simone MariniDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Chase A PaganiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Philip J SpreadboroughDepartment of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Cassie J RoweDepartment of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Pauline YuDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Annie MeiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Noelle VisserDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Shuli LiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Geoffrey E HespeDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Amanda K HuberDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Amy L StrongDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Miriam A ShelefDivision of Rheumatology, University of Wisconsin and William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Jason S KnightDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Thomas A DavisDepartment of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Benjamin LeviDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
University of Michigan–Ann Arbor · USUniformed Services University of the Health Sciences · USThe University of Texas Southwestern Medical Center · USWilliam S. Middleton Memorial Veterans Hospital · US

Funding

TRAINING PROGRAM IN ORGANOGENESIST32HD007505 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PASCA DI MAGLIANO, MARINA, SPENCE, JASON · 1997 to 2021
$6.9M
Targeting Molecular and Cellular Mediators of Inflammation to Prevent Pathologic Cell Differentiation and Heterotopic OssificationR01AR071379 · NIAMS · UT SOUTHWESTERN MEDICAL CENTER · PI LEVI, BENJAMIN · 2017 to 2021
$1.5M
Developing New Diagnostic and Timed, TAK1 Specific Treatment Strategies for Trauma Induced Heterotopic OssificationR01GM123069 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI LEVI, BENJAMIN · 2017 to 2020
$1.2M
PAD2 and PAD4 in Citrullination, Autoantibodies, and Rheumatoid ArthritisK08AR065500 · NIAMS · UNIVERSITY OF WISCONSIN-MADISON · PI SHELEF, MIRIAM ANNE · 2014 to 2018
$690k
HHS | National Institutes of Health (NIH) R01AR071379HHS | National Institutes of Health (NIH) R01GM123069HHS | National Institutes of Health (NIH) T32-HD007505Howard Hughes Medical InstituteNIAMS NIH HHS K08 AR065500NIAMS NIH HHS R01 AR071379NICHD NIH HHS T32 HD007505NIGMS NIH HHS R01 GM123069U.S. Department of Defense (DOD) W81XWH-18-1-0653 (OR170174)
6 · The paper itself

Abstract

Ischemia reperfusion (IR) injury results in devastating skeletal muscle fibrosis. Here, we recapitulate this injury with a mouse model of hindlimb IR injury which leads to skeletal muscle fibrosis. Injury resulted in extensive immune infiltration with robust neutrophil extracellular trap (NET) formation in the skeletal muscle, however, direct targeting of NETs via the peptidylarginine deiminase 4 (PAD4) mechanism was insufficient to reduce muscle fibrosis. Circulating levels of IL-10 and TNFα were significantly elevated post injury, indicating toll-like receptor (TLR) signaling may be involved in muscle injury. Administration of hydroxychloroquine (HCQ), a small molecule inhibitor of TLR7/8/9, following injury reduced NET formation, IL-10, and TNFα levels and ultimately mitigated muscle fibrosis and improved myofiber regeneration following IR injury. HCQ treatment decreased fibroadipogenic progenitor cell proliferation and partially inhibited ERK1/2 phosphorylation in the injured tissue, suggesting it may act through a combination of TLR7/8/9 and ERK signaling mechanisms. We demonstrate that treatment with FDA-approved HCQ leads to decreased muscle fibrosis and increased myofiber regeneration following IR injury, suggesting short-term HCQ treatment may be a viable treatment to prevent muscle fibrosis in ischemia reperfusion and traumatic extremity injury.

Indexed as

AnimalsCell ProliferationDisease Models, AnimalExtracellular TrapsFibrosisInterleukin-10MaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMuscle, SkeletalMuscular DiseasesNeutrophilsProtein-Arginine Deiminase Type 4Reperfusion InjurySignal TransductionInterleukin-10Protein-Arginine Deiminase Type 4Toll-Like ReceptorsTumor Necrosis Factor-alphaextracellular signal-regulated kinases (ERK) 1/2hydroxychloroquineinflammationmuscle fibrosis

Identifiers

PMID33089917
PMCPMC8054227
OpenAlexW3094074015

What OpenQuestion holds

Textmetadata
LicenceTDM
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.