Omics · study · 2026
NAT10 Promotes Vascular Remodeling via mRNA Ac4c Acetylation
Listed in NCBI GEO
Vascular smooth muscle cells (VSMCs) phenotype switching is a pathological hallmark in various cardiovascular diseases.
Description
N4-acetylcytidine (ac4C), catalyzed by N-acetyltransferase 10 (NAT10), is well conserved in the enzymatic modification of RNA. NAT10-mediated ac4C acetylation is involved in various physiological and pathological processes, including cardiac remodeling.
However, the biological functions and underlying regulatory mechanisms of mRNA ac4C modifications in vascular diseases remain elusive. By combining in vitro and in vivo vascular injury models, we identified NAT10 as a crucial protein involved in the promotion of postinjury neointima formation as well as VSMCs proliferation. The potential mechanisms of NAT10 in vascular neointima formation were clarified by RNA sequence (RNA-seq), acetylated mRNA immunoprecipitation sequence (acRIP-seq), and RNA binding protein immunoprecipitation sequence (RIP-seq).
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NAT10 and ac4C modification were upregulated in injured human and rodent arteries. Deletion of NAT10 in VSMCs effectively reduces postinjury neointima formation and VSMCs phenotype switching. Further RNA-seq, RIP-seq, and acRIP-seq revealed that NAT10, by its ac4C modification, directly interacts with genes, including integrin-β1 (ITGB1) and collagen type I alpha 2 chain (Col1a2) mRNAs.
NAT10-mediated ac4C consequently increased ITGB1 mRNA stability and its downstream focal adhesion kinase (FAK) signaling, thereby directly influencing the proliferation of VSMCs and vascular remodeling. The regulation of NAT10 on VSMC phenotype is of translational significance because administration of remodelin, a NAT10 inhibitor, effectively prevents neointima formation by suppressing VSMCs proliferation and downregulating of ITGB1 expression and deactivating its FAK signaling.
Our study reveals that NAT10 promotes vascular remodeling via mRNA Ac4c acetylation, which may be a promising therapeutic target against vascular remodeling.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE272nnn/GSE272001 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272001 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1134350 ncbi.nlm.nih.gov/bioproject/PRJNA1134350 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Other · Rattus norvegicus
- From keywords
- Life Sciences
- Inferred from text
- Cardiac remodeling 75% · Heart 65% · RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE272001 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:cardiac-remodeling | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10116 | 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 |