イチハラ　アツヒロ   ICHIHARA Atsuhiro   市原　淳弘    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.
掲載誌名	正式名：American journal of physiology. Renal physiology 略　 称：Am J Physiol Renal Physiol ISSNコード：15221466(Electronic)15221466(Linking)
巻・号・頁	pp.ajprenal.00088.2016
著者・共著者	Ramkumar Nirupama†, Stuart Deborah, Mironova Elena, Bugay Vladislav, Wang Shuping, Abraham Nikita, ICHIHARA Atsuhiro, Stockand James D, Kohan Donald E
発行年月	2016/04
概要	UNASSIGNED:The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 month of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+)excretion and investigaUNASSIGNED:ted the signaling mechanisms by which PRR regulates Na(+)balance. No detectable differences in BP were observed between control and PRR KO mice fed normal or low Na(+)diets. However, compared to controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na(+)balance with normal and low Na(+)intake. PRR KO mice had an attenuated hypertensive response and reduced Na(+)retention following angiotensin-II infusion. Further, PRR KO mice had significantly lower epithelial Na(+)channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT-1, ERK1/2 or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na(+)wasting and reduces the hypertensive response to Ang-II.
DOI	10.1152/ajprenal.00088.2016
PMID	27053687