Omics · study · 2026
ClC-Kb deficiency inhibits the proliferation and mitochondrial metabolism of renal tubules
Listed in NCBI GEO
Our previous study demonstrates that ClC-Kb chloride channel deficiency in Bartter syndrome (BS) type 3 not only impairs transport activity but also affects the development of the thick ascending limbs (TALs) and possibly distal convoluted tubules (DCTs).
Description
This developmental defect is important to the pathogenesis of BS, with unknown underlying mechanisms. This study investigated the cellular effects of ClC-Kb deficiency and explored potential therapeutic strategies addressing these effects.
We isolated TALs and DCTs from Clc-k2(ClC-Kb mouse ortholog)-knockout (Clc-k2-/-) and wild-type mice for multi-omics analyses. The results revealed differential regulations involving cell cycle, cell proliferation, mitochondrial respiration, and metabolism. In vitro studies showed that Clc-k2-/- TALs proliferated less efficiently than wild-type cells, exhibited a G2/M cell cycle delay, had reduced mitochondrial mass and oxidative phosphorylation alongside the suppressed glycolysis and fatty acid oxidation.
Read the rest (1 more)
A gain-of-function D561A mutation in with-no-lysine kinase 4 (WNK4), known to stimulate transepithelial salt transport and mitochondrial biogenesis in TALs/DCTs, significantly restored the salt transport in Clc-k2-/- TALs/DCTs and improved the phenotype of BS. Alternatively, overexpressing Pgc1α, a master activator of mitochondrial biogenesis, also alleviated the disease severity in Clc-k2-/- mice. These findings provide insights into the molecular mechanisms of BS type 3 and suggest novel therapeutic approaches.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307980 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307980 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1327916 ncbi.nlm.nih.gov/bioproject/PRJNA1327916 ↗
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 | GSE307980 | 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[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 |