Omics · study · 2026
Podnl1 as a novel contributor to HIV-associated pulmonary vascular disease
Listed in NCBI GEO
Thanks to the advent of combination antiretroviral therapy (cART), life expectancy has noticeably increased in people with HIV (PWH); however, they also display an elevated susceptibility to developing severe pulmonary vascular disease (PVD).
Description
Despite efforts to understand the role of HIV-encoded proteins in the pathogenesis of the disease, the underlying mechanisms remain to be elucidated. Using three mouse models of HIV and in vitro cell studies, we tested the hypothesis that HIV-related proteins induce PVD via Podnl1-dependent mechanisms.
We reported that the expression of HIV proteins in Tg26 mice and bone marrow transplant from Tg26 to wild-type mice promotes the development of PVD with no sex differences. RNAseq and qPCR analysis revealed, for the first time, high expression of Podnl1 in the lungs of our HIV models. Strikingly, lung specimens from PWH on cART exhibit higher Podnl1 levels compared to HIV- individuals.
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We also revealed that the observed cardiopulmonary alterations and expression levels of Podnl1 were more pronounced in aged intact Tg26 mice. In addition, Podnl1 overexpression resulted in increased collagen-I production and PASMCs proliferation. Remarkably, we found that HIV-Tat is the only viral protein detectable in peripheral blood mononuclear cells obtained from PWH on cART, and chronic exposure of mice to HIV-Tat recapitulated the cardiopulmonary complications of intact and BMT Tg26 mice.
We provide the first evidence that HIV-Tat and Podnl1 are important contributing factors to PVD related to HIV infection, which presents potential new therapeutic avenues for the prevention of HIV-associated cardiopulmonary complications.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331101 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331101 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1466905 ncbi.nlm.nih.gov/bioproject/PRJNA1466905 ↗
project · from NCBI GEO
- PubMed 42657694 pubmed.ncbi.nlm.nih.gov/42657694 ↗
publication · 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 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE331101 | 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: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 |