Excel · study · 2026
ALKBH3 inhibition normalizes neovessels by reprogramming endothelial fate in diabetic microvasculopathy
Listed in NCBI GEO
Diabetic microvasculopathy is a serious diabetes complication, with diabetic retinopathy (DR) being a leading cause of blindness worldwide due to immature, leaky neovessels.
Description
Anti-angiogenic therapies merely suppress neovascularization, leaving the retina oxygen-starved and prone to regrowth. Thus, therapies that stabilize aberrant neovessels are needed.
We identify the RNA demethylase ALKBH3 as an epitranscriptional driver of diabetic microvasculopathy. Upregulated ALKBH3 in diabetic vascular endothelial cells promoted a pathological shift to an unstable, pro-angiogenic phenotype, disrupting blood-retinal barrier and forming immature neovessels, which impaired vision. Conversely, removing ALKBH3 protected against this.
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Mechanistically, ALKBH3 demethylated BMP2 mRNA to increase its stability via YTHDF2. We further developed a neovasculature-targeting nanoparticle delivering the ALKBH3 inhibitor HUHS015, which normalized retinal neovascularization by simultaneously limiting growth and promoting maturation. It acted synergistically with VEGF blockade, suggesting potential for anti-VEGF-resistant cases.
Our work defines ALKBH3 as a key mediator of diabetic microvasculopathy and supports a VEGF-independent therapeutic paradigm that shifts the focus from vessel suppression to active normalization.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331464 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331464 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1468192 ncbi.nlm.nih.gov/bioproject/PRJNA1468192 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE331464 | 15 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[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 |