Omics · study · 2026
ANGPTL3 in podocytes contributes to pathogenesis of lupus nephritis by activating MSR1 in macrophage
Listed in NCBI GEO
Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is driven by immune complex deposition and inflammatory renal injury.
Description
This study uncovers a novel mechanism in which podocyte-derived angiopoietin-like protein 3 (ANGPTL3) exacerbates LN pathogenesis through macrophage scavenger receptor 1 (MSR1)-mediated activation. Protein interaction screening revealed direct binding between ANGPTL3 and MSR1, a macrophage-enriched receptor.
Clinical analyses demonstrated elevated glomerular expression of ANGPTL3 and MSR1 in LN patients, correlating with reduced renal function and histopathological damage. In vitro, ANGPTL3-overexpressing podocytes activated macrophages in an MSR1-dependent manner. RNA sequencing of ANGPTL3-stimulated bone marrow-derived macrophages (BMDMs) identified robust activation of interferon signaling pathways, with key genes (Tnip3, Isg20).
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Silencing Msr1 abolished these effects, suppressing interferon-related gene expression. In the pristane-induced lupus model, ANGPTL3 and MSR1 co-localized with infiltrating macrophages in injured glomeruli, mirroring human LN pathology. These findings establish the ANGPTL3-MSRI axis as a critical driver of macrophage activation and interferon signaling in LN, highlighting ANGPTL3 as a promising therapeutic target to mitigate immune-mediated renal injury in SLE.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302297 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302297 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1289818 ncbi.nlm.nih.gov/bioproject/PRJNA1289818 ↗
project · from NCBI GEO
- PubMed 41883862 pubmed.ncbi.nlm.nih.gov/41883862 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE302297 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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 |