Excel · study · 2026
VHL Loss Orchestrates Pro-Tumor Microenvironment Through BMP10-Induced CXCL13 Signaling in Renal Lymphatics [RNA-Seq]
Listed in NCBI GEO
Clear-cell renal cell carcinoma (ccRCC) is frequently associated with loss of the tumor suppressor gene VHL.
Description
To investigate the early events of ccRCC pathogenesis, we generated a conditional mouse model with Vhlh deletion in renal tubular epithelial cells. The model exhibited key histopathological features reminiscent of human ccRCC, including epithelial disorganization, immune infiltration, and vascular remodeling.
VhlhloxP/loxP mice were crossed with Hoxb7-Cre-GFP mice to induce kidney tubule-specific Vhlh deletion. Kidney tissue was analyzed using histology, immunofluorescence, immunohistochemistry, and flow cytometry. Proliferation, immune infiltration, vascular and lymphatic architecture, as well as functional drainage assays and gene expression profiling, were conducted to characterize phenotypic changes.
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Vhlh-deficient kidneys exhibited clear-cell morphology, tubular hypertrophy, and a ~ 4-fold increase in Ki67⁺ epithelial proliferation compared to wild-type controls. Immune cell (CD45⁺) infiltration and endothelial cell (CD31⁺) expansion were significantly elevated. Lymphatic architecture was disrupted, with increased numbers of Pdpn⁺ cells, and impaired lymphatic drainage was observed by Evans Blue Dye retention.
Pdpn⁺ lymphatic cells expressed high levels of CXCL13, which was validated in both mouse and human ccRCC tissues. BMP10, produced by Vhlh-deficient epithelium, appeared to act through Alk1 signaling to induce CXCL13 expression. CXCL13 in turn promoted proliferation, migration, EMT activation in VHL-deficient epithelial cells via CXCR5.
Genetic deletion of CXCL13 or pharmacologic inhibition of Alk1 reduced lymphatic remodeling, inflammation, and epithelial proliferation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE308nnn/GSE308286 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308286 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1330062 ncbi.nlm.nih.gov/bioproject/PRJNA1330062 ↗
project · from NCBI GEO
- PubMed 42589645 pubmed.ncbi.nlm.nih.gov/42589645 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE308286 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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: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 |