Proteomics

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Arhgef11 high and low salt kidney proteomic analysis


ABSTRACT: Arhgef11 is a Rho guanine nucleotide exchange factor previously implicated in kidney injury in the Dahl salt-sensitive rat (SS-WT). Through exchange of GDP for GTP, Arhgef11 regulates cytoskeletal structure, function, and cell-cell contacts through a variety of stimuli (e.g., G-protein coupled receptors, growth factors, and shear stress). We studied the SS-Arhgef11-/- rat model at 4-12 weeks of age under low and high salt (0.3% or 2% NaCl). To better understand the molecular mechanisms associated with renal protection from loss of Arhgef11, MS/MS proteomics was performed on kidney from SS-Arhgef11-/- and SS-WT at week 12 (low-salt). At week 12, 1017 genes and 363 proteins were observed. In summary, in vivo phenotyping provides strong evidence that increased Arhgef11 expression in the Dahl S rat leads to actin cytoskeleton mediated changes in cell morphology and cell function (impaired reuptake filtered protein) that promote kidney injury, hypertension, and decline in kidney function.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Kidney

SUBMITTER: Elizabeth Flynn  

LAB HEAD: Elizabeth Flynn

PROVIDER: PXD011758 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

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

Johnson Ashley C AC   Wu Wenjie W   Attipoe Esinam M EM   Sasser Jennifer M JM   Taylor Erin B EB   Showmaker Kurt C KC   Kyle Patrick B PB   Lindsey Merry L ML   Garrett Michael R MR  

Hypertension (Dallas, Tex. : 1979) 20200309 4


<i>Arhgef11</i> 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 <i>Arhgef11</i> expression in an SS-<i>Arhgef11</i><sup>SHR</sup>-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 contr  ...[more]

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