Loss of Arhgef11 in the Dahl Salt-Sensitive Rat Protects Against Hypertension-Induced Renal Injury.

Hypertension
Ashley C JohnsonMichael R Garrett

Abstract

Arhgef11 is a Rho-guanine nucleotide exchange factor that was previously implicated in kidney injury in the Dahl salt-sensitive (SS) rat, a model of hypertension-related chronic kidney disease. Reduced Arhgef11 expression in an SS-Arhgef11SHR-minimal congenic strain (spontaneously hypertensive rat allele substituted for S allele) significantly decreased proteinuria, fibrosis, and improved renal hemodynamics, without impacting blood pressure compared with the control SS (SS-wild type). Here, SS-Arhgef11-/- and SS-wild type rats were placed on either low or elevated salt (0.3% or 2% NaCl) from 4 to 12 weeks of age. On low salt, starting at week 6 and through week 12, SS-Arhgef11-/- animals demonstrated a 3-fold decrease in proteinuria compared with SS-wild type. On high salt, beginning at week 6, SS-Arhgef11-/- animals demonstrated >2-fold lower proteinuria from weeks 8 to 12 and 30 mm Hg lower BP compared with SS-wild type. To better understand the molecular mechanisms of the renal protection from loss of Arhgef11, both RNA sequencing and discovery proteomics were performed on kidneys from week 4 (before onset of renal injury/proteinuria between groups) and at week 12 (low salt). The omics data sets revealed loss of Arhgef11 (SS...Continue Reading

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Citations

May 5, 2020·Trends in Genetics : TIG·Michael R Garrett, Ron Korstanje
Apr 4, 2021·International Journal of Molecular Sciences·Wakako Kawarazaki, Toshiro Fujita
Apr 21, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Josef ZichaIvana Vaněčková

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Datasets Mentioned

BETA
PRJNA600744
PXD011758

Methods Mentioned

BETA
urine collections
ELISA
urine collection
RNAseq
PCR
FCS
flow cytometry
GTPases

Software Mentioned

Bio
Nikon Elements
FCS express
Rad Maestro
Enrichr
GraphPad Prism

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