DOI

10.17077/etd.l1uiq5yk

Document Type

Thesis

Date of Degree

Summer 2014

Degree Name

MS (Master of Science)

Degree In

Pharmacology

First Advisor

Sigmund, Curt D

First Committee Member

Grobe, Justin L

Second Committee Member

Kwitek, Anne E

Abstract

Renin (REN) expression is required to maintain blood pressure and electrolyte homeostasis. However, the mechanisms by which REN is transcriptionally regulated remain elusive. We reported a functional role for several nuclear receptors (NRs) on REN gene transcription. To identify other candidate NRs that regulate REN, we analyzed a publicly available microarray dataset (GUDMAP Developing Kidney ST1) to compare the expression pattern of REN and the 48 NRs across different kidney cell types. Our analysis revealed 14 NRs exhibiting a similar pattern as REN. We hypothesized that these NRs are co-regulated with REN and can regulate REN transcription. To test this hypothesis, we set up 2 cohorts of mice in which REN expression was either high or low compared to control mice and measured expression of REN and NRs in renal cortex by qPCR. The high-REN cohort was given the ACE inhibitor captopril (100g/kg/day) for 10 days, and the low-REN group was implanted subcutaneously with a deoxycorticosterone acetate pellet (50mg) and received 0.15 M NaCl in drinking water for 21 days (DOCA-salt) in addition to water. Captopril increased REN and reduced NR2F6 expression relative to vehicle treatment (REN: 16±1, p

Pages

ix, 68 pages

Bibliography

Includes bibliographical references (pages 50-62).

Copyright

Copyright 2014 Ko-Ting Lu

Included in

Pharmacology Commons

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