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Title page for ETD etd-03212017-115324


Type of Document Dissertation
Author Norlander, Allison Elizabeth
Author's Email Address allison.e.norlander@vanderbilt.edu
URN etd-03212017-115324
Title SGK1, influenced by salt and IL-17A, promotes hypertension and end-organ damage
Degree PhD
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
Alyssa Hasty Committee Chair
Jacek Hawiger Committee Member
Jens Titze Committee Member
Katherine Murray Committee Member
Raymond Harris Committee Member
Keywords
  • immunology
  • hypertension
  • kidney
Date of Defense 2017-03-15
Availability unrestricted
Abstract
Hypertension is a leading cause of cardiovascular morbidity and mortality, leading to myocardial infarction, heart failure, stroke, and chronic kidney disease. We have previously shown that the pro-inflammatory cytokine interleukin-17A (IL-17A) plays a critical role in angiotensin II-induced hypertension and vascular dysfunction. Additionally, many studies have demonstrated a link between increased dietary salt intake and hypertension. Recently, excess salt has been shown to promote the differentiation of CD4+ T cells into pathogenic IL-17A-producing Th17 cells via a serum and glucocorticoid-regulated kinase 1 (SGK1) dependent pathway in CD4+ T cells. Classically, SGK1 is known to play an important role in the stabilization of distal sodium transporters in the kidney. Thus, we sought to investigate the role of T cell SGK1 in the development of hypertension and the mechanism by which IL17A promotes renal dysfunction in hypertension. We found that T cell SGK1 is essential for the maintenance of both angiotensin II and deoxycorticosterone acetate (DOCA) salt-induced hypertension. T cell SGK1 deficient mice exhibited blunted blood pressure, abrogated renal/vascular inflammation, and preserved renal/vascular function in response to hypertensive stimuli. Moreover, we found that IL-17A regulates proximal and distal tubule sodium transporters in the kidney via an SGK1 dependent pathway. Together, these data demonstrate that IL-17A and SGK1 may be important therapeutic targets for hypertension.

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