Omics · study · 2026
Nintedanib and Pirfenidone affect growth and differentiation of human alveolar type 2 cells
Listed in NCBI GEO
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease characterized by epithelial cell senescence.
Description
Pirfenidone and nintedanib are approved drugs for the treatment of IPF. They significantly slow disease progression, but their mechanisms of action, especially on Alveolar type 2 (AT2) cells, are poorly understood.
We addressed this question by evaluating colony formation and growth of human AT2 cells co-cultured with fibroblasts in organoid culture in the presence of pirfenidone and nintedanib. We further evaluated molecular changes induced by these drugs via single cell RNA-seq of treated organoids. Results.
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AT2 cell organoids cultured in the presence of pirfenidone or nintedanib resulted in increased colony formation and, in the case of nintedanib, in larger colonies. We observed that untreated or pirfenidone treated AT2 cells lost surfactant protein C (SFTPC) expression and acquired an expression profile consistent with keratin (KRT)17high/KRT5- basaloid cells, whereas a larger proportion of nintedanib treated cells retained SFTPC expression.
In contrast, AT2 cells treated with TGFb inhibitor exhibited intermediate (SFTPC-/KRT17low) gene expression profile. Conclusion. These results suggest that nintedanib prevents transdifferentiation of AT2 cells to KRT17+/KRT5- cells in culture and likely acts proximal to TGFb.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE322nnn/GSE322959 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322959 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1432010 ncbi.nlm.nih.gov/bioproject/PRJNA1432010 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE322959 | 15 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[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 |