Omics · study · 2026
Deletion of P311 enhances regeneration in aged skeletal muscle
Listed in NCBI GEO
While aging results in marked decreases in the capacity of skeletal muscle to repair following injury, as well as increases in fibrosis, the pathways and factors that regulate these processes are poorly defined.
Description
P311/Nrep (P311) is a highly conserved protein known to promote fibrosis through TGF-beta production in non-muscle tissues. Considering the over-production of TGF-beta in aged muscle, especially in the context of regeneration, we aimed to determine if the loss of P311 would enhance aged muscle regeneration.
To test this hypothesis, we utilized a chemical injury (BaCl2) model to injure the tibialis anterior (TA) muscle in young (4-7 months) and old (24 months) wild-type and global P311 knockout mice (P311-/-). In wild-type mice, P311 expression increased in response to injury in young muscle and to an even greater extent in aged muscle. P311-deficiency decreased TGF-β production, particularly in old muscle tissue.
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P311-deficiency also decreased fibrosis in old mice, including improved histology and reductions in fibrotic gene markers. Regeneration as assessed by fiber regrowth and force generation was increased in old mice with P311-deficiency, and genetic programs that drive skeletal muscle regeneration were enriched in old P311-/- mice relative to old wild-type mice. Single-cell transcriptomic analysis revealed P311 was found to be highly expressed in skeletal muscle fibroblast and fibroadipogenic progenitor (FAP) populations.
The loss of P311 in aged muscle FAPs was sufficient to reduce their fibrogenic capacity. These findings establish P311 as a therapeutic target to enhance aged muscle regeneration through reductions in fibrosis and related fibrogenic pathways.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329069 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329069 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1457493 ncbi.nlm.nih.gov/bioproject/PRJNA1457493 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE329069 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |