Omics · study · 2026
Systemic and Proximal Tubule Specific Knockout of Arhgef11 and Impact on Hypertension and Kidney Injury
Listed in NCBI GEO
Hypertension is a progressive condition that predisposes patients to the development of chronic kidney disease (CKD).
Description
Previous genetic and animal studies utilizing the Dahl salt-sensitive (SS) rat, a genetic model of progressive hypertension and CKD, identified that Arhgef11 was playing a role in hypertension and CKD in the Dahl SS model. Arhgef11 is a Rho guanine nucleotide exchange factor involved in the regulation of the cytoskeleton, intracellular trafficking, protein-protein interactions, and transcription factor regulation.
Temporal evaluation of SS-WT and SS-Arhgef11-/- rats demonstrated that the loss of Arhgef11 attenuated hypertension and improved renal function. Transcriptome and proteomic studies lead to the hypothesis that dysregulation of these pathways in the kidney, particularly the proximal tubule, may alter sodium handling and ultimately lead to hypertension. Current rat studies confirmed previous work between SS-WT and SS-Arhgef11-/- and investigated early (week 4) transcriptional changes using single nuclei RNA sequencing, present before blood pressure differences are observed.
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Due to only being able to test systemic loss of Arhgef11 in the rat model, a global knockout (Arhgef11-/-(CMV)), as well as a proximal tubule-specific deletion (Arhgef11-/-(Sglt2)) were studied in the mouse. Studies utilized two models of experimental hypertension: Angiotensin II and deoxycorticosterone acetate (DOCA) + salt. Both models demonstrated a slight protective effect on blood pressure and kidney injury for DOCA experimental models, replicating the rat knockout data.
However, the impact of the loss of Arhgef11 was dependent on the type of induced hypertension, with the large effect in the rat model likely explained by the highly permissive genetic background of the Dahl SS model.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333422 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333422 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1471075 ncbi.nlm.nih.gov/bioproject/PRJNA1471075 ↗
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% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE333422 | 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: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 |