Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes

Physiological Genomics
Lesley A GrahamSandosh Padmanabhan

Abstract

Previously, our comprehensive cardiovascular characterization study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesized at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod-/- mice have significantly lower blood pressure than Umod+/+ mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed use RNA-Seq to delineate salt stress pathways in tubules isolated from Umod+/+ mice (a model of sodium retention) and Umod-/- mice (a model of sodium depletion) ± 300 mosmol sodium chloride ( n = 3 per group). In response to salt stress, the tubules of Umod+/+ mice displayed an upregulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, P = 2.48 e-12) and Hspa1b (Log2 fold change 4.05, P = 2.48 e-12). This response was absent in tubules of Umod-/- mice. Interestingly, seven of the genes discordantly expressed in the ...Continue Reading

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Citations

Jun 18, 2019·Current Opinion in Nephrology and Hypertension·Matthias T F WolfMingzhu Nie
Feb 9, 2020·Journal of the American Society of Nephrology : JASN·Jing LiuAndrew P McMahon
Sep 21, 2021·Frontiers in Cardiovascular Medicine·Ruilian YouLimeng Chen
Sep 28, 2021·Frontiers in Medicine·Babak YazdaniMarcus E Kleber

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Methods Mentioned

BETA
PCR
RNA-Seq
electrophoresis
chip

Software Mentioned

Cutadapt
DESeq2
Bioconductor package
Kallisto
R package BiomaRt
R package Piano
Piano

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