Omics · study · 2026
SGK1 Mediates TGF-β1-Induced Epithelial-Mesenchymal Transition and Fibrosis in Experimental Bronchiolitis Obliterans
Listed in NCBI GEO
Bronchiolitis obliterans (BO) represents a major complication limiting long-term survival after lung transplantation, with epithelial-mesenchymal transition (EMT) serving as a core pathogenic mechanism.
Description
The TGF-β1 signaling pathway plays a critical role in EMT induction and can activate serum/glucocorticoid-regulated kinase 1 (SGK1) expression. While SGK1 is upregulated in various fibrotic diseases, its functional significance in BO remains undefined.
To elucidate SGK1's role in post-transplant BO fibrosis and its interaction with the TGF-β1 pathway, we established a murine heterotopic tracheal transplantation model. Histopathological evaluation and RNA sequencing demonstrated significant SGK1 upregulation in BO lesions by day 28. In vitro, both pharmacological inhibition (EMD638683) and genetic knockdown of SGK1 (siRNA) attenuated TGF-β1-induced EMT in the human small airway epithelial cell line (HSAECs), while concurrently suppressing the expression of extracellular matrix genes (COL1 and FN1).
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Furthermore, SGK1 inhibition reduced TGF-β1-induced SMAD2/3 phosphorylation. Therapeutic administration of EMD638683, initiated after disease establishment, significantly ameliorated BO pathology. These findings demonstrate that SGK1 promotes BO-associated fibrosis through TGF-β1-mediated EMT and ECM deposition, identifying SGK1 as a potential therapeutic target for post-transplant BO intervention.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334327 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334327 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1474801 ncbi.nlm.nih.gov/bioproject/PRJNA1474801 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE334327 | 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 (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |