Identification of Aldosterone-Induced Transcripts in the Distal Tubule of Mouse Kidney Public Deposited

Aldosterone acts via the mineralocorticoid receptor to regulate transcription of genes encoding aldosterone-induced proteins. In the aldosterone-sensitive distal nephron and collecting duct of the kidney, these proteins regulate the activity of the epithelial sodium channel ENaC, resulting in increased channel activity and sodium retention. Many aldosterone-induced proteins have been identified by transcriptional profiling of cell culture models; however, deletion of these proteins in mice does not produce the phenotype of renal sodium wasting, elevated plasma potassium, and low blood pressure observed in mice with deletion of the mineralocorticoid receptor specifically in the kidney epithelium. Thus, aldosterone-induced proteins essential for the activation of ENaC remain to be identified.

This dissertation sought to identify these proteins using two studies designed to overcome the limitations of previous screens. In the first study, distal tubule cells were isolated from the kidneys of wild-type mice fed low sodium or high sodium diet. The distal tubule cells were used for RNA-seq to identify salt-sensitive transcripts that were differentially expressed between the two groups. Distal tubule cells isolated from mouse kidney were used in this study to avoid the limitations of in vitro cell culture models. Manipulation of endogenous aldosterone by changing dietary sodium was chosen to avoid the hypokalemic metabolic alkalosis that develops with the administration of aldosterone in vivo.

  • swanson.elizabeth.2019.pdf
Publication Date
  • 2019
Document type