Renin cells with defective Gsα/cAMP signaling contribute to renal endothelial damage

Pflügers Archiv : European journal of physiology
Anne SteglichVladimir T Todorov

Abstract

Synthesis of renin in renal renin-producing cells (RPCs) is controlled via the intracellular messenger cAMP. Interference with cAMP-mediated signaling by inducible knockout of Gs-alpha (Gsα) in RPCs of adult mice resulted in a complex adverse kidney phenotype. Therein, glomerular endothelial damage was most striking. In this study, we investigated whether Gsα knockout leads to a loss of RPCs, which itself may contribute to the endothelial injury. We compared the kidney phenotype of three RPC-specific conditional mouse lines during continuous induction of recombination. Mice expressing red fluorescent reporter protein tdTomato (tdT) in RPCs served as controls. tdT was also expressed in RPCs of the other two strains used, namely with RPC-specific Gsα knockout (Gsα mice) or with RPC-specific diphtheria toxin A expression (DTA mice, in which the RPCs should be diminished). Using immunohistological analysis, we found that RPCs decreased by 82% in the kidneys of Gsα mice as compared with controls. However, the number of tdT-positive cells was similar in the two strains, demonstrating that after Gsα knockout, the RPCs persist as renin-negative descendants. In contrast, both renin-positive and tdT-labeled cells decreased by 80% in DTA ...Continue Reading

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Citations

Apr 2, 2021·Circulation Research·Maria Luisa S Sequeira-Lopez, R Ariel Gomez

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Methods Mentioned

BETA
transgenic
biopsy
biopsies
ELISA
Flow Cytometry

Software Mentioned

Ensembl
SeQC
FIJI ( ImageJ
GraphPad Prism
IHW
DESeq2
GraphPad
FastQC
R
GSNAP

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