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	Enhanced intrarenal receptor-mediated prorenin activation in chronic progressive anti-thymocyte serum nephritis rats on high salt intake.
掲載誌名	正式名：American journal of physiology. Renal physiology 略　 称：Am J Physiol Renal Physiol ISSNコード：1522-1466(Electronic)1522-1466(Linking)
巻・号・頁	303(1),pp.F130-8
著者・共著者	Yanjie Huang†, YAMAMOTO Tatsuo, MISAKI Taro, SUZUKI Hiroyuki, TOGAWA Akashi, OHASHI Naro, FUKASAWA Hirotaka, FUJIGAKI Yoshihide, ICHIHARA Atsuhiro, NISHIYAMA Akira, SENBONMATSU Takaaki, IKEGAYA Naoki, HISHIDA Akira
発行年月	2012/07
概要	Despite suppression of the circulating renin-angiotensin system (RAS), high salt intake (HSI) aggravates kidney injury in chronic kidney disease. To elucidate the effect of HSI on intrarenal RAS, we investigated the levels of intrarenal prorenin, renin, (pro)renin receptor (PRR), receptor-mediated prorenin activation, and ANG II in chronic anti-thymocyte serum (ATS) nephritic rats on HSI. Kidney fibrosis grew more severe in the nephritic rats on HSI than normal salt intake. Despite suppression of plasma renin and ANG II, marked increases in tubular prorenin and renin proteins without concomitant rises in renin mRNA, non-proteolytically activated prorenin, and ANG II were noted in the nephritic rats on HSI. Redistribution of PRR from the cytoplasm to the apical membrane, along with elevated non-proteolytically activated prorenin and ANG II, was observed in the collecting ducts and connecting tubules in the nephritic rats on HSI. Olmesartan decreased cortical prorenin, non-proteolytically activated prorenin and ANG II, and apical membranous PRR in the collecting ducts and connecting tubules, and attenuated the renal lesions. Cell surface trafficking of PRR was enhanced by ANG II and was suppressed by olmesartan in Madin-Darby canine kidney cells. These data suggest the involvement of the ANG II-dependent increase in apical membrane PRR in the augmentation of intrarenal binding of prorenin and renin, followed by nonproteolytic activation of prorenin, enhancement of renin catalytic activity, ANG II generation, and progression of kidney fibrosis in the nephritic rat kidneys on HSI. The origin of the increased tubular prorenin and renin remains to be clarified. Further studies measuring the urinary prorenin and renin are needed.
DOI	10.1152/ajprenal.00275.2011
文献番号	22496409