Salt-sensitive transcriptome of isolated kidney distal tubule cells

Abstract

In the distal kidney tubule, the steroid hormone aldosterone regulates sodium reabsorption via the epithelial sodium channel (ENaC). Most studies seeking to identify ENaC-regulating aldosterone-induced proteins have used transcriptional profiling of cultured cells. To identify salt-sensitive transcripts in an in vivo model, we used low-NaCl or high-NaCl diet to stimulate or suppress endogenous aldosterone, in combination with magnetic- and fluorescence-activated cell sorting to isolate distal tubule cells from mouse kidney for transcriptional profiling. Of the differentially expressed transcripts, 162 were more abundant in distal tubule cells isolated from mice fed low-NaCl diet, and 161 were more abundant in distal tubule cells isolated from mice fed high-NaCl diet. Enrichment analysis of Gene Ontology biological process terms identified multiple statistically overrepresented pathways among the differentially expressed transcripts that were more abundant in distal tubule cells isolated from mice fed low-NaCl diet, including ion transmembrane transport, regulation of growth, and negative regulation of apoptosis. Analysis of Gene Ontology molecular function terms identified differentially expressed transcription factors, transmembrane transporters, kinases, and G protein-coupled receptors. Finally, comparison with a recently published study of gene expression changes in distal tubule cells in response to administration of aldosterone identified 18 differentially expressed genes in common between the two experiments. When expression of these genes was measured in cortical collecting ducts microdissected from mice fed low-NaCl or high-NaCl diet, eight were differentially expressed. These genes are likely to be regulated directly by aldosterone and may provide insight into aldosterone signaling to ENaC in the distal tubule.

The single-cell transcriptomic landscape of early human diabetic nephropathy

“…There was decreased expression of the Na + /Ca++ exchanger, encoded by SLC8A1 , which has been reported in experimental models of diabetes (30), and evidence for alteration of SLIT-ROBO signaling with an increase in ROBO2 and a decrease in SLIT2 . Interestingly, we detected a statistically significant overlap between a curated list of 908 aldosterone (31–34) and salt-sensitive (35) transcripts with the differentially expressed genes detected in the thick ascending limb, late distal convoluted tubule, and principal cells, suggestive of conserved response to aldosterone signaling (Dataset S10).…”

Sex Differences in Blood Pressure and the Kidney Cortex Transcriptome in Nonhuman Primates

“…We demonstrated consistency in kidney biopsy cell composition, diet, both time of day and duration of collection of telemetry data between females and males -all indicating that differences in the study design did not account for kidney transcriptome differences. In addition, we showed sex differences in the primate kidney transcriptome (2,(35)(36)(37). WGCNA of kidney cortex RNA-Seq data was used as an unbiased approach to identify sex-speci c transcripts correlated with BP.…”

Sex Differences in Blood Pressure and the Kidney Cortex Transcriptome in Nonhuman Primates

“…Sex differences were observed in 24 We demonstrated consistency in kidney biopsies by cell composition, diet, as well as both time of day and duration of collection of telemetry data between females and males -all indicating that differences in the study design did not account for kidney transcriptome differences. In addition, we showed sex differences in the primate kidney transcriptome (2,(35)(36)(37). WGCNA of kidney cortex RNA-Seq data was used as an unbiased approach to identify sex-speci c transcripts correlated with BP.…”