Omics · study · 2026
ZNF469 promotes human lung fibrosis via transcriptionally regulating extracellular matrix genes
Listed in NCBI GEO
Pulmonary fibrosis (PF) is a chronic lung disease defined by excessive deposition of extracellular matrix (ECM) components, leading to remodeling of lung structural architerture and impaired repiratory function.
Description
Chronically activated resident fibroblasts are considered one of major cellular source of aberrant ECM accumulation; however, their precise cellular origins and the initiating events that drive their persistent activation remain incompletely understood.
Emerging evidence has identified zinc finger protein 469 (ZNF469) as a novel pro-fibrotic transcription factor in hepatic stellate cells and dermal fibroblasts, where it drives ECM gene expression and fibrogenic remodeling, suggesting a potentially conserved role across fibrotic tissues. With short hairpin-mediated doxycycline inducible system, ZNF469 knockdown LFs are employed to explore its ficbrotic potential in LFs.
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Depletion of ZNF469 resulted in marked impairment of LF proliferation and migratory capacity, accompanied by reduced collagen production and secretion. Transcriptomic profiling further revealed significant downregulation of ECM-associated pathways following ZNF469 knockdown, supporting a conserved role for ZNF469 in fibroblast-driven fibrogenesis. Consistently, CUT&RUN analysis demonstrated direct binding of ZNF469 to the promoters of a broad spectrum of ECM-related genes in LFs.
Collectively, these findings uncover a previously unrecognized regulatory role of ZNF469 as a key pro-fibrotic transcription factor in lung fibroblasts and highlight its potential as a promising therapeutic target for pulmonary fibrosis.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318606 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318606 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1419306 ncbi.nlm.nih.gov/bioproject/PRJNA1419306 ↗
project · from NCBI GEO
- PubMed 42206677 pubmed.ncbi.nlm.nih.gov/42206677 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE318606 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | 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[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 |