Omics · study · 2026
Global knockout of melanoma differentiation-associated protein 5 protects mice from chronic hypoxia/SU5416-induced pulmonary hypertension
Listed in NCBI GEO
Pulmonary arterial hypertension (PAH) is a severe disease affecting the pulmonary arteries, causing increased blood pressure due to narrowing of the pulmonary artery lumen.
Description
Aberrant proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs), along with a dysregulation of the immune response, contributes to arterial remodeling. We hypothesized that the cytosolic RNA receptor melanoma differentiation-associated protein 5 (MDA5) contributes to PAH by dysregulating pulmonary vascular cell function and immune cell response.
In lung tissue from control patients and PAH patients, MDA5 immunoreactivity was widely distributed throughout the pulmonary artery wall. After exposing whole-body MDA5-/- mice to the chronic hypoxia/SU5416 (Hx/Su) protocol, we detected reduced right ventricular systolic pressure and pulmonary artery media wall thickness compared to wild-type mice. Pro-inflammatory mediators, interferon-regulated genes, and perivascular accumulation of CD11b+ myeloid cells were decreased in the lung tissue of Hx/Su-exposed MDA5-/- mice.
Read the rest (2 more)
In cultured human pulmonary artery ECs, MDA5 gene silencing disrupted DNA synthesis and angiogenic network formation. Bulk RNA sequencing analysis revealed the differential expression of 2,533 genes, affecting gene ontologies such as immune response, cell cycle, and cholesterol metabolism. Analysis of a publicly available single-cell RNA-sequence dataset indicates increased expression of MDA5 in monocytes/macrophages in pulmonary arteries from patients with PAH, which is associated with an interferon gene signature.
Knockdown of MDA5 in macrophage-like cells reduced the type I interferon gene signature. Our data suggest a protective effect of whole-body MDA5 knockout in mice, which may be due to reduced immune dysregulation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314466 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314466 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1391371 ncbi.nlm.nih.gov/bioproject/PRJNA1391371 ↗
project · from NCBI GEO
- PubMed 42030239 pubmed.ncbi.nlm.nih.gov/42030239 ↗
publication · 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 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE314466 | 14 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: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 |