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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.

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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.

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Life Sciences
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Disease 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33432715 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title