The (pro)renin receptor. A decade of research: what have we learned?

Krop, Manne; Lu, Xifeng; Danser, A.H. Jan; Meima, Marcel E

doi:10.1007/s00424-012-1105-z

Cited by 66 publications

(53 citation statements)

References 107 publications

(167 reference statements)

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“…It is evident that PRR acts in a renin-independent manner in low vertebrates (1,37,(39)(40)(41)). PRR appears to be similarly involved in the regulation of embryogenesis in mammals, as evidenced by the lethal phenotype in mice with systemic or tissue-specific deletion of PRR (1,4).…”

Section: Induction Of Diabetes Insipidus and Suppression Of Renal Prrmentioning

confidence: 99%

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

135

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The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the antidiuretic action of sPRR and its potential interaction with liver X receptors (LXRs), which are known regulators of urine-concentrating capability. Water deprivation consistently elevated urinary sPRR excretion in mice and humans. A template-based algorithm for protein-protein interaction predicted the interaction between sPRR and frizzled-8 (FZD8), which subsequently was confirmed by coimmunoprecipitation. A recombinant histidine-tagged sPRR (sPRR-His) in the nanomolar range induced a remarkable increase in the abundance of renal aquaporin 2 (AQP2) protein in primary rat inner medullary collecting duct cells. The AQP2 up-regulation relied on sequential activation of FZD8-dependent β-catenin signaling and cAMP-PKA pathways. Inhibition of FZD8 or tankyrase in rats induced polyuria, polydipsia, and hyperosmotic urine. Administration of sPRR-His alleviated the symptoms of diabetes insipidus induced in mice by vasopressin 2 receptor antagonism. Administration of the LXR agonist TO901317 to C57/BL6 mice induced polyuria and suppressed renal AQP2 expression associated with reduced renal PRR expression and urinary sPRR excretion. Administration of sPRR-His reversed most of the effects of TO901317. In cultured collecting duct cells, TO901317 suppressed PRR protein expression, sPRR release, and PRR transcriptional activity. Overall we demonstrate, for the first time to our knowledge, that sPRR exerts antidiuretic action via FZD8-dependent stimulation of AQP2 expression and that inhibition of this pathway contributes to the pathogenesis of diabetes insipidus induced by LXR agonism.soluble (pro)renin receptor | liver X receptor | aquaporin-2 | frizzled-8 | β-catenin F ull-length (Pro)renin receptor (PRR), a 350-amino acid transmembrane receptor for prorenin and renin, is subjected to protease-mediated cleavage to produce a 28-kDa protein of the N-terminal extracellular domain, the soluble (pro)renin receptor (sPRR), and the 8.9-kDa C-terminal intracellular domain called "M8.9" (1, 2). Before the cloning of full-length PRR in mesangial cells as an integral 39-kDa membrane protein (3), M8.9 was identified as a truncated protein associated with the vacuolar H + -ATPase (V-ATPase) from bovine chromatin granules (4). The cleavage occurs in Golgi apparatus through furin (5) or ADMA19 (6). An sPRR ELISA kit has been developed to detect sPRR in plasma and urine samples (7) . With this assay, increased serum sPRR levels have been demonstrated in patients with heart failure (8), kidney disease (9, 10), hypertension (11), and preeclampsia (2). Moreover, serum sPRR is positively associated with serum creatinine, blood urea nitrogen, and urine protein and is inversely associated with the estimated glomerular filtration rate in patients with chronic kidney disease caused by hypertension...

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Section: Induction Of Diabetes Insipidus and Suppression Of Renal Prrmentioning

confidence: 99%

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

135

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“…Moreover, the discovery of a prorenin/renin receptor [86], which can be activated by the enzymatically inactive prorenin and by renin independently of the formation of angiotensin, highlights the fact that the RAAS cascade is much more complex and exerts more biological effects than initially thought and depicted in most textbooks. These "nonclassical" renin-angiotensin pathways have been the subject of recent excellent reviews [5,52,65,92]. Moreover, RAAS components are expressed in various tissues, suggesting that local RAAS systems, acting in a paracrine or autocrine manner, exist in addition to the circulating RAAS.…”

Section: Introductionmentioning

confidence: 98%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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The renin-angiotensin-aldosterone system (RAAS) is a central element in the control of the salt and water balance of the body and arterial blood pressure. The activity of the RAAS is controlled by the protease renin, which is released from renal juxtaglomerular epithelioid cells (JGE cells) into the circulation. Renin release is regulated by a complex interplay of several locally acting hormones or mechanisms and longer feedback loops one of which involves salt intake. Acute NaCl loads or longer lasting high salt intakes suppress plasma renin activity, whereas reductions in NaCl intake stimulate it. Because the activation of the RAAS conserves the salt content of the body, a classical feedback loop between salt intake/body salt content and renin is established. Despite of its important role for body fluid homeostasis, the precise signaling pathways connecting salt intake with the synthesis and release of renin are only incompletely understood. Four putative controllers of the salt-dependent regulation of the RAAS have been suggested: (1) the macula densa mechanism which adjusts renin release in response to changes in the renal tubular salt concentration; (2) salt-dependent changes in the arterial blood pressure; (3) circulating salt-dependent hormones, particularly the atrial natriuretic peptide (ANP); and (4) renal sympathetic nervous activity, which is regulated by extracellular volume and arterial blood pressure. In this review, the role of these known controllers of the RAAS will be discussed with special emphasis on their relative contributions to the salt-dependent regulation of the RAAS at different time frames.

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“…További érdekes tény, hogy RAS-gátló szerekkel (beleértve a renint gátló aliskirent is) kezelt betegekben megemelkedik a plazma reninszintje [40]. Feldman és mtsai diabeteses patkányokban vizsgálták az aliskiren reninre kifejtett hatását [41].…”

Section: Terápiás Konzekvenciákunclassified

The cortical collecting duct plays a pivotal role in kidney local renin-angiotensin system

et al. 2013

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A renin-angiotenzin rendszer szervezetünk egyik legjelentősebb hormonális rendszere, amelynek juxtaglomerularis apparátusban történő szabályozása és szerepe jól ismert. Jelen összefoglaló a vese embrionális fejlődésével párhuza-mot állítva a gyűjtőcsatorna renintermelését írja le, valamint ennek lokális szerepét és terápiás célpontként szolgáló lehetőségeit igyekszik feltárni. Nemrégiben került leírásra, hogy krónikus angiotenzin-II-kezelés során, két vese-, egy klip modellben, illetve diabetes mellitusban a gyűjtőcsatorna jelenti az intrarenalis (pro)renintermelés legfőbb helyét. Ebben a lokalizációban a (pro)renin előtt út nyílhat az interstitialis renin-angoitenzin rendszer komponensek, a szisztémás keringés és a nemrégiben leírásra került (pro)reninreceptor felé. A (pro)renin saját receptorán keresztül intracelluláris profi broticus utakat képes aktiválni, így egyúttal potenciálisan új célpontja lehet a hypertoniához kapcsolódó vagy diabeteses nephropathia kezelésének, illetve eszköze a krónikus vesekárosodást előidéző folyamatok korai diagnosztizálásának. Orv. Hetil., 2013, 154, 643-649. Kulcsszavak: renin-angiotenzin rendszer, gyűjtőcsatorna, (pro)renin, nephropathia, embriogenezisThe cortical collecting duct plays a pivotal role in kidney local renin-angiotensin systemThe renin-angiotensin system is one of the most important hormone systems in the body, and the regulations as well as the role in the juxtaglomerular apparatus are well known. The present review focuses on renin secretion in a recently described localization, the cortical collecting duct. The authors display it in parallel of the copying strategy of an adult and a developing kidney. Furthermore, based on different animal studies it highlights the local role of renin released from the collecting duct. In chronic angiotensin II-infused, 2-kidney, 1-clip hypertensive model as well as in diabetic rats the major source of (pro)renin is indeed the collecting duct. In this localization this hormone can reach both the systemic circulation and the interstitial renin-angiotensin system components including the newly described (pro)renin receptor, by which (pro)renin is able to locally activate pro-fi brotic intracellular signal pathways. Consequently, one can postulate that in the future renin may serve either as a new therapeutic target in nephropathy associated with both hypertension and diabetes or as an early diagnostic marker in chronic diseases leading to nephropathy. Orv. Hetil., 2013, 154, 643-649. Keywords: renin-angiotensin system, collecting duct, (pro)renin, nephropathy, embryogenesis (Beérkezett: 2013. március 4.; elfogadva: 2013. március 28.) Rövidítések 2K1C = (2-kidney, 1-clip model) két vese-, egy klipmodell; ACE = (angiotensin converting enzyme) angiotenzinkonvertáló enzim; ANG = angiotenzinogén; Ang-I = angiotenzin-I; Ang-II = angiotenzin-II; ARB = angiotenzinreceptor-blokkoló; AT1R = 1-es típusú angiotenzinreceptor; DM = diabetes mellitus; ENaC = epithelialis Na + -csatorna; ERK = (extracellular regulated kinaz) extracellulár...

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The (pro)renin receptor. A decade of research: what have we learned?

Cited by 66 publications

References 107 publications

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

Salt feedback on the renin-angiotensin-aldosterone system

The cortical collecting duct plays a pivotal role in kidney local renin-angiotensin system

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