Evidence map›Paper›PMID 39455585›Full record

ArticleNature communications2024

Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury.

Pihu Mehrotra, James Jablonski, John Toftegaard, Yali Zhang, Shahryar Shahini, Jianmin Wang, Carey W Hung, Reilly Ellis, Gabriella Kayal, Nika Rajabian and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2024. 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
–field-weighted citation impact
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.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Pihu MehrotraDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA.ORCID 0000-0001-9369-5013
James JablonskiDepartment of Department of Rehabilitation Science, University at Buffalo, Buffalo, NY, 14214, USA.
John ToftegaardDepartment of Biomedical Engineering, University at Buffalo, NY, Buffalo, NY, 14260, USA.
Yali ZhangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA.
Shahryar ShahiniDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA.ORCID 0000-0003-3813-6424
Jianmin WangDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA.ORCID 0000-0001-7527-0409
Carey W HungBiomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Blacksburg, VA, 24060, USA.
Reilly EllisBiomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Blacksburg, VA, 24060, USA.
Gabriella KayalBiomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Blacksburg, VA, 24060, USA.
Nika RajabianDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA.ORCID 0000-0002-9963-4024
Song LiuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA.
Kelly C S RoballoBiomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Blacksburg, VA, 24060, USA.
Susan B UdinDepartment of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203, USA.ORCID 0000-0001-5542-6314
Stelios T AndreadisDepartment of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA. sandread@buffalo.edu.ORCID 0000-0001-9885-0457
Kirkwood E PersoniusDepartment of Department of Rehabilitation Science, University at Buffalo, Buffalo, NY, 14214, USA. kep7@buffalo.edu.ORCID 0000-0001-6391-2953

Funding

Restoring the regenerative capacity of the aged muscleR01AG068250 · NIA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI ANDREADIS, STELIOS THEOHARIS · 2020 to 2024
$2.0M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01AG068250NIA NIH HHS R01 AG068250
6 · The paper itself

Abstract

Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. PNI is characterized by nerve degeneration distal to the site of nerve injury resulting in long periods of skeletal muscle denervation. During this period, muscle fibers atrophy and frequently become incapable of "accepting" innervation because of the slow speed of axon regeneration post injury. We hypothesize that reprogramming the skeletal muscle to an embryonic-like state may preserve its reinnervation capability following PNI. To this end, we generate a mouse model in which NANOG, a pluripotency-associated transcription factor is expressed locally upon delivery of doxycycline (Dox) in a polymeric vehicle. NANOG expression in the muscle upregulates the percentage of Pax7+ nuclei and expression of eMYHC along with other genes that are involved in muscle development. In a sciatic nerve transection model, NANOG expression leads to upregulation of key genes associated with myogenesis, neurogenesis and neuromuscular junction (NMJ) formation. Further, NANOG mice demonstrate extensive overlap between synaptic vesicles and NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, NANOG mice show greater improvement in motor function as compared to wild-type (WT) animals, as evidenced by improved toe-spread reflex, EMG responses and isometric force production. In conclusion, we demonstrate that reprogramming muscle can be an effective strategy to improve reinnervation and functional outcomes after PNI.

Indexed as

Muscle, SkeletalNanog Homeobox ProteinNerve RegenerationNeuromuscular JunctionPeripheral Nerve InjuriesAnimalsCellular ReprogrammingDisease Models, AnimalDoxycyclineFemaleMaleMiceMice, Inbred C57BLMice, TransgenicMuscle DevelopmentNeurogenesisDoxycyclineNanog Homeobox ProteinNanog protein, mousePAX7 Transcription FactorReceptors, Cholinergic

Identifiers

PMID39455585
PMCPMC11511891

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.