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Prorenin receptor

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https://www.readbyqxmd.com/read/28396529/brain-renin-angiotensin-system-does-it-exist
#1
Bibi S van Thiel, Alexandre Góes Martini, Luuk Te Riet, David Severs, Estrellita Uijl, Ingrid M Garrelds, Frank P J Leijten, Ingrid van der Pluijm, Jeroen Essers, Fatimunnisa Qadri, Natalia Alenina, Michael Bader, Ludovit Paulis, Romana Rajkovicova, Oliver Domenig, Marko Poglitsch, A H Jan Danser
Because of the presence of the blood-brain barrier, brain renin-angiotensin system activity should depend on local (pro)renin synthesis. Indeed, an intracellular form of renin has been described in the brain, but whether it displays angiotensin (Ang) I-generating activity (AGA) is unknown. Here, we quantified brain (pro)renin, before and after buffer perfusion of the brain, in wild-type mice, renin knockout mice, deoxycorticosterone acetate salt-treated mice, and Ang II-infused mice. Brain regions were homogenized and incubated with excess angiotensinogen to detect AGA, before and after prorenin activation, using a renin inhibitor to correct for nonrenin-mediated AGA...
April 10, 2017: Hypertension
https://www.readbyqxmd.com/read/28373410/bradykinin-b2-receptor-activation-regulates-renin-in-m-1-cells-via-protein-kinase-c-and-nitric-oxide
#2
Lucienne S Lara, Camille R T Bourgeois, Samir S El-Dahr, Minolfa C Prieto
In the collecting duct (CD), the interactions of renin angiotensin system (RAS) and kallikrein-kinin system (KKS) modulate Na(+) reabsorption, volume homeostasis, and blood pressure. In this study, we used a mouse kidney cortical CD cell line (M-1 cells) to test the hypothesis that in the CD, the activation of bradykinin B2 receptor (B2R) increases renin synthesis and release. Physiological concentrations of bradykinin (BK) treatment of M-1 cells increased renin mRNA and prorenin and renin protein contents in a dose-dependent manner and increased threefold renin content in the cell culture media...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28367520/therapeutic-targets-of-renin-angiotensin-system-in-ocular-disorders
#3
REVIEW
Rajesh Choudhary, Mandeep Singh Kapoor, Amrita Singh, Surendra H Bodakhe
PURPOSE: To review current literature on the renin-angiotensin system (RAS)-mediated pathogenic mechanisms and therapeutic targets in ocular diseases. METHODS: A comprehensive literature survey was performed on PubMed, Scopus, and Google Scholar databases published from 1977 to 2016. The search terms were a RAS, angiotensin, angiotensin receptor, prorenin, pro (renin) receptor, angiotensin converting enzyme inhibitor, angiotensin receptor blocker associated with ocular disorders like cataract, glaucoma, diabetic retinopathy (DR), macular degeneration, and uveitis...
March 2017: Journal of Current Ophthalmology
https://www.readbyqxmd.com/read/28359068/the-effect-of-combined-treatment-with-the-pro-renin-receptor-blocker-hrp-and-quinapril-in-type-1-diabetic-rats
#4
Gábor Kökény, Lilla Fang, Csaba Révész, Miklós M Mózes, Péter Vörös, Gábor Szénási, László Rosivall
BACKGROUND/AIMS: Diabetic nephropathy remains a major clinical problem. The effects of prorenin might be adverse, but the literature data are controversial. We compared the renal effects of the (pro)renin receptor ((P)RR) blockade and angiotensin converting enzyme (ACE) inhibition on the progression of diabetic nephropathy in rats. METHODS: Diabetes (DM) was induced by ip. streptozotocin administration in adult male Sprague-Dawley rats, followed by eight weeks of treatment with the (P)RR blocker "handle region" decoy peptide (HRP, 0,1 mg/kg/day) or with the ACE inhibitor Quinapril (Q, 50 mg/kg/day) and grouped as follows: 1...
April 3, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28276504/pathologic-roles-of-receptor-associated-prorenin-system-in-idiopathic-epiretinal-membrane
#5
Yoko Dong, Atsuhiro Kanda, Kousuke Noda, Wataru Saito, Susumu Ishida
Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent signaling via (P)RR. The aim of this study is to determine the association of RAPS with idiopathic epiretinal membrane (iERM). Reverse transcription-PCR indicated the expression of RAPS components, including (P)RR and Ang II type 1 receptor (AT1R), in iERM tissues and human Müller glial cell line. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for glial fibrillary acidic protein, a marker for glial cells, and co-localized with prorenin and angiotensinogen, respectively...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193701/osteoblastic-lrp4-promotes-osteoclastogenesis-by-regulating-atp-release-and-adenosine-a2ar-signaling
#6
Lei Xiong, Ji-Ung Jung, Hao-Han Guo, Jin-Xiu Pan, Xiang-Dong Sun, Lin Mei, Wen-Cheng Xiong
Bone homeostasis depends on the functional balance of osteoblasts (OBs) and osteoclasts (OCs). Lrp4 is a transmembrane protein that is mutated in patients with high bone mass. Loss of Lrp4 in OB-lineage cells increases bone mass by elevating bone formation by OBs and reducing bone resorption by OCs. However, it is unclear how Lrp4 deficiency in OBs impairs osteoclastogenesis. Here, we provide evidence that loss of Lrp4 in the OB lineage stabilizes the prorenin receptor (PRR) and increases PRR/V-ATPase-driven ATP release, thereby enhancing the production of the ATP derivative adenosine...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28161727/expression-of-angiotensinogen-and-receptors-for-angiotensin-and-prorenin-in-the-rat-and-monkey-striatal-neurons-and-glial-cells
#7
Pablo Garrido-Gil, Ana I Rodriguez-Perez, Patricia Fernandez-Rodriguez, Jose L Lanciego, Jose L Labandeira-Garcia
The renin-angiotensin system (RAS) was initially considered as a circulating humoral system, which function is the regulation of blood pressure. However, it is now known that there exists local RAS in many tissues, including brain. In recent studies, we have demonstrated the presence of a local RAS in the substantia nigra of rodents and primates that modulates dopamine release and dopamine receptor expression. However, overactivation of local RAS exacerbates neuroinflammation, oxidative stress and dopaminergic cell death...
February 4, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28090037/expression-of-pro-renin-receptor-during-rapamycin-induced-erythropoiesis-in-k562-erythroleukemia-cells-and-its-possible-dual-actions-on-erythropoiesis
#8
Kiriko Kaneko, Koji Ohba, Takuo Hirose, Kazuhito Totsune, Kazumichi Furuyama, Kazuhiro Takahashi
(Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is expressed in erythroblastic cells. (P)RR has multiple biological actions: prorenin activation, stimulation of the intracellular signaling including extracellular signal-regulated kinases, and functional complex formation with vacuolar H(+)-ATPase (v-ATPase). However, the functional implication of (P)RR in erythroblast cells has not been clarified. The aim of the present study was to clarify changes of (P)RR expression during erythropoiesis and a role of (P)RR in the heme synthesis...
January 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28031172/prorenin-receptor-controls-renal-branching-morphogenesis-via-wnt-%C3%AE-catenin-signaling
#9
Renfang Song, Adam Janssen, Yuwen Li, Samir S El-Dahr, Ihor V Yosypiv
The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H+-ATPase. Renal branching morphogenesis, defined as growth and branching of the ureteric bud (UB), is essential for mammalian kidney development. Previously, we demonstrated that conditional ablation of the PRR in the UB in PRRUB-/- mice causes severe defects in UB branching, resulting in marked kidney hypoplasia at birth. Here, we investigated UB transcriptome using whole-genome-based analysis of gene expression in UB cells FACS-isolated from PRRUB-/- and control kidneys at birth (P0) to determine the primary role of the PRR in terminal differentiation and growth of UB-derived collecting ducts...
December 28, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28005703/do-prorenin-synthesizing-cells-release-active-open-prorenin
#10
Alexandre G Martini, Manne Krop, Langeza Saleh, Ingrid M Garrelds, A H Jan Danser
BACKGROUND: The function of prorenin, the inactive precursor of renin, remains unclear after many decades of research. The discovery of a (pro)renin receptor suggested that prorenin, by binding to this receptor, would become active, that is, obtain an 'open' conformation. However, the receptor only interacted with prorenin at levels that were many orders of magnitude above its normal levels, making such interaction in-vivo unlikely. Prorenin occurs in two conformations, an open, active form, and a closed, inactive form...
February 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27956412/expression-of-renin-angiotensin-system-ras-components-in-endometrial-cancer
#11
Sarah J Delforce, Eugenie R Lumbers, Celine Corbisier de Meaultsart, Yu Wang, Anthony Proietto, Geoffrey Otton, Jim Scurry, Nicole M Verrills, Rodney J Scott, Kirsty G Pringle
A dysfunctional endometrial renin-angiotensin system (RAS) could aid the growth and spread of endometrial cancer. To determine if the RAS is altered in endometrial cancer, we measured RAS gene expression and protein levels in 30 human formalin-fixed, paraffin-embedded (FFPE) endometrioid carcinomas and their adjacent endometrium. All components of the RAS were expressed in most tumours and in adjacent endometrium; mRNA levels of (pro)renin receptor (ATP6AP2), angiotensin II type 1 receptor (AGTR1), angiotensin-converting enzyme (ACE1) and angiotensin-converting enzyme 2 (ACE2) mRNA levels were greater in tumour tissue than adjacent non-cancerous endometrium (P = 0...
January 2017: Endocrine Connections
https://www.readbyqxmd.com/read/27761002/intrarenal-renin-angiotensin-system-activity-is-augmented-after-initiation-of-dialysis
#12
Naro Ohashi, Shinsuke Isobe, Sayaka Ishigaki, Takahisa Suzuki, Masafumi Ono, Tomoyuki Fujikura, Takayuki Tsuji, Akihiko Kato, Seiichiro Ozono, Hideo Yasuda
Circulating renin-angiotensin system (RAS) activation is maintained after renal function has deteriorated. The activation of the intrarenal RAS plays a critical role in the pathophysiology of chronic kidney disease (CKD), independently of the circulating RAS. However, the activation of intrarenal RAS and the chymase-dependent pathway after initiation of dialysis has not been clarified. We recruited 19 CKD patients (10 without dialysis and 9 with dialysis) who underwent a heminephrectomy. Circulating RAS was investigated before nephrectomy...
April 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27689008/adipose-tissue-p-rr-regulates-insulin-sensitivity-fat-mass-and-body-weight
#13
Zulaykho Shamansurova, Paul Tan, Basma Ahmed, Emilie Pepin, Ondrej Seda, Julie L Lavoie
OBJECTIVE: We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. METHODS: An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27688999/mechanisms-underlying-prorenin-actions-on-hypothalamic-neurons-implicated-in-cardiometabolic-control
#14
Soledad Pitra, Yumei Feng, Javier E Stern
BACKGROUND: Hypertension and obesity are highly interrelated diseases, being critical components of the metabolic syndrome. Despite the growing prevalence of this syndrome in the world population, efficient therapies are still missing. Thus, identification of novel targets and therapies are warranted. An enhanced activity of the hypothalamic renin-angiotensin system (RAS), including the recently discovered prorenin (PR) and its receptor (PRR), has been implicated as a common mechanism underlying aberrant sympatho-humoral activation that contributes to both metabolic and cardiovascular dysregulation in the metabolic syndrome...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27534754/high-potassium-promotes-mutual-interaction-between-pro-renin-receptor-and-the-local-renin-angiotensin-aldosterone-system-in-rat-inner-medullary-collecting-duct-cells
#15
Chuanming Xu, Hui Fang, Li Zhou, Aihua Lu, Tianxin Yang
(Pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD) with unclear functional implication. It is not known whether CD PRR is regulated by high potassium (HK). Here, we aimed to investigate the effect of HK on PRR expression and its role in regulation of aldosterone synthesis and release in the CD. In primary rat inner medullary CD cells, HK augmented PRR expression and soluble PPR (sPRR) release in a time- and dose-dependent manner, which was attenuated by PRR small interfering RNA (siRNA), eplerenone, and losartan...
October 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27490783/neuroinflammatory-mechanisms-of-hypertension-potential-therapeutic-implications
#16
Pawel J Winklewski, Marek Radkowski, Urszula Demkow
PURPOSE OF REVIEW: Inflammation of forebrain and hindbrain nuclei has recently been highlighted as an emerging factor in the pathogenesis of neurogenic hypertension. The aim of this review is to summarize the state of the art in this field and to discuss recently discovered pathophysiological mechanisms, opening new perspectives for therapeutic application. RECENT FINDINGS: Microglia Toll-like receptor 4 causally links angiotensin II (AngII)-mediated microglia cell activation and oxidative stress within the hypothalamic paraventricular nucleus (PVN)...
September 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27458124/prorenin-renin-receptor-blockade-promotes-a-healthy-fat-distribution-in-obese-mice
#17
Paul Tan, Carolane Blais, Thi M-D Nguyen, Peter W Schiller, Jolanta Gutkowska, Julie L Lavoie
OBJECTIVE: Administration of the handle region peptide (HRP), a (pro)renin receptor blocker, decreases body weight gain and visceral adipose tissue (VAT) in high-fat/high-carbohydrate (HF/HC) diet-fed mice. The objective of this study was to elucidate potential mechanisms implicated in these observations. METHODS: Mice were given a normal or a HF/HC diet along with saline or HRP for 10 weeks. RESULTS: In HF/HC-fed mice, HRP increased the expression of several enzymes implicated in lipogenesis and lipolysis in subcutaneous fat (SCF) while the expression of the enzyme implicated in the last step of lipogenesis decreased in VAT...
September 2016: Obesity
https://www.readbyqxmd.com/read/27419631/prorenin-receptor-acts-as-a-potential-molecular-target-for-pancreatic-ductal-adenocarcinoma-diagnosis
#18
Arivajiagane Arundhathi, Wen-Han Chuang, Jen-Kun Chen, Shin-E Wang, Yi-Ming Shyr, Jiun-Yu Chen, Wei-Neng Liao, Hsin-Wei Chen, Yi-Min Teng, Chiao-Chih Pai, Chih-Hong Wang
Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells...
July 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27372447/recent-updates-on-the-proximal-tubule-renin-angiotensin-system-in-angiotensin-ii-dependent-hypertension
#19
REVIEW
Xiao C Li, Jia L Zhuo
It is well recognized that the renin-angiotensin system (RAS) exists not only as circulating, paracrine (cell to cell), but also intracrine (intracellular) system. In the kidney, however, it is difficult to dissect the respective contributions of circulating RAS versus intrarenal RAS to the physiological regulation of proximal tubular Na(+) reabsorption and hypertension. Here, we review recent studies to provide an update in this research field with a focus on the proximal tubular RAS in angiotensin II (ANG II)-induced hypertension...
August 2016: Current Hypertension Reports
https://www.readbyqxmd.com/read/27350190/water-deprivation-increases-pro-renin-receptor-levels-in-the-kidney-and-decreases-plasma-concentrations-of-soluble-pro-renin-receptor
#20
Yuma Tamura, Nobuyoshi Mori, Bin Xu, Takahiro Nakamura, Seiko Yamakoshi, Takuo Hirose, Osamu Ito, Kazuhito Totsune, Kazuhiro Takahashi, Masahiro Kohzuki
Water deprivation activates the renin-angiotensin system. We have hypothesized that the renal expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, could be changed under dehydration. Moreover, plasma levels of soluble (P)RR (s(P)RR) comprising of the extracellular domain of (P)RR may reflect the renal (P)RR expression. In the present study, we therefore aimed to clarify changes of plasma s(P)RR concentrations and kidney tissue (P)RR levels using rats with dehydration. Male Wister-Kyoto rats were divided into two groups; dehydrated (DH) rats deprived of water for 72 hours with free access to food, and control rats...
2016: Tohoku Journal of Experimental Medicine
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