Omics · study · 2026
ALDH2 inhibition reprograms tubular epithelial cell metabolism and promotes renal injury susceptibility
Listed in NCBI GEO
Tubular epithelial cells (TECs), viewed as the initiating factor in renal fibrosis, undergo a transition from re-absorptive to pro-fibrotic phenotype during chronic kidney disease (CKD) progression.
Description
Serving as a critical energy source, Free fatty acid (FFA) metabolism disruption results in injured TECs. Nevertheless, mechanisms underlying pathological FFA metabolism in injured TECs remain unclear.
We observed an inverse correlation between ALDH2 expression in TECs and lipid deposition in the renal tissues from CKD patients. To determine whether ALDH2 protects against fibrosis via regulating FFA metabolism, we generated TEC–specific ALDH2 knockout (Aldh2TEC-KO) mice, and observed exacerbated fibrosis and lipid deposition in the renal tissues of Aldh2TEC-KO mice in two different CKD models. Mechanically, we verified that ALDH2 facilitated the formation of PPARα/RXRα heterodimer via nuclear translocation, while ALDH2 deficiency hindered that process, suppressed PPARα/RXRα complex activation, and disrupted fatty acid oxidation.
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Notably, Fenofibrate, the PPARα-specific agonist, failed to alleviate fibrosis or lipid deposition in the renal tissues from Aldh2TEC-KO mice, indicating that ALDH2 deficiency attenuated Fenofibrate's efficacy. Furthermore, the ALDH2 E487K mutation similarly impaired FFA metabolism and promoted fibrotic phenotype. Together, this work uncovers ALDH2 as a novel FAO regulator and an influencing factor of Fenofibrate therapeutic efficacy in CKD.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306861 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306861 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1312710 ncbi.nlm.nih.gov/bioproject/PRJNA1312710 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE306861 | 12 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[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 |