Omics · study · 2026
Targeting NAT10 to surpress ferroptosis and attenuate skin fibrosis progression
Listed in NCBI GEO
Description
Background
N-acetyltransferase 10 (NAT10) is a unique RNA acetyltransferase responsible for catalyzing N4-acetylcytidine (ac4C) modifications on mRNA, influencing RNA stability and translation. While NAT10 has been implicated in fibrosis of other organs, its role in skin fibrosis and ferroptosis regulation remains poorly understood. This study aimed to investigate the involvement of NAT10 in fibroblast activation and skin fibrotic remodeling via modulation of ferroptosis.
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Methods
The expression of NAT10 was assessed in bleomycin-induced fibrotic mouse skin tissues and TGF-β1-stimulated fibroblasts. Functional experiments, including wound healing, transwell migration, and EdU staining, were performed following NAT10 knockdown. The impact of NAT10 on ferroptosis was evaluated by measuring lipid ROS, GSH, and MDA levels, along with key ferroptosis markers such as GPX4, SLC7A11, and TFR1.
RNA-seq and bioinformatic analyses identified MAP1LC3A as a downstream target. The effects of NAT10 inhibition were further validated in vivo using Remodelin and Erastin interventions. Results: NAT10 expression and ac4C RNA modification were upregulated in fibrotic skin tissues and activated fibroblasts.
Silencing NAT10 impaired fibroblast proliferation and migration, alleviated fibrosis, and reduced ferroptosis-related oxidative stress both in vitro and in vivo. Mechanistically, NAT10 knockdown decreased MAP1LC3A stability, leading to suppressed ferroptosis. Pharmacological modulation with Erastin partially reversed the antifibrotic effects of NAT10 inhibition, underscoring the involvement of ferroptosis in this process.
Conclusions: Our findings demonstrate that NAT10 contributes to skin fibrosis by promoting ferroptosis through the regulation of MAP1LC3A stability. Targeting NAT10 may offer a promising therapeutic approach for fibrotic skin diseases. Keywords: Skin Fibrosis, Ferroptosis, NAT10, Fibroblast
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297275 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297275 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1262100 ncbi.nlm.nih.gov/bioproject/PRJNA1262100 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE297275 | 13 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | 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 |