dc.creator | Norlander, Allison Elizabeth | |
dc.date.accessioned | 2020-08-21T21:19:40Z | |
dc.date.available | 2019-03-29 | |
dc.date.issued | 2017-03-29 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03212017-115324 | |
dc.identifier.uri | http://hdl.handle.net/1803/11007 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | immunology | |
dc.subject | hypertension | |
dc.subject | kidney | |
dc.title | SGK1, influenced by salt and IL-17A, promotes hypertension and end-organ damage | |
dc.type | dissertation | |
dc.contributor.committeeMember | Raymond Harris | |
dc.contributor.committeeMember | Jacek Hawiger | |
dc.contributor.committeeMember | Katherine Murray | |
dc.contributor.committeeMember | Jens Titze | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Molecular Physiology and Biophysics | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2019-03-29 | |
local.embargo.lift | 2019-03-29 | |
dc.contributor.committeeChair | Alyssa Hasty | |