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Prorenin receptor

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https://www.readbyqxmd.com/read/28814438/collecting-duct-prorenin-receptor-knockout-reduces-renal-function-increases-na-excretion-and-mitigates-renal-responses-in-angii-induced-hypertensive-mice
#1
Minolfa C Prieto, Virginia Reverte, Mykola Mamenko, Marta Kuczeriska, Luciana C Veiras, Carla B Rosales, Matthew McLellan, Oliver Gentile, V Behrana Jensen, Atsuhiro Ichihara, Alicia A McDonough, Oleh M Pochynyuk, Alexis A Gonzalez
Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANGII-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial...
August 16, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28701311/pge2-upregulates-renin-through-e-prostanoid-receptor-1-via-pkc-camp-creb-pathway-in-m-1-cells
#2
Alexis A Gonzalez, Nicolas Salinas-Parra, Dan Leach, L Gabriel Navar, Minolfa C Prieto
During the early phase of angiotensin (ANG) II-dependent hypertension tubular prostaglandin E2 (PGE2) is increased. Renin synthesis and secretion in the collecting duct (CD) is upregulated by ANGII contributing to further intratubular ANGII formation. However, what happens first and whether the triggering mechanism is independent of tubular ANGII, remain unknown. PGE2 stimulates renin synthesis in juxtaglomerular (JG) cells via E-prostanoid (EP) receptors through cAMP/CREB pathway. EP receptors are also expressed in the CD...
July 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28696542/-pro-renin-receptor-activation-increases-profibrotic-markers-and-fibroblast-like-phenotype-through-mapk-dependent-ros-formation-in-mouse-renal-collecting-duct-cells
#3
Alexis A Gonzalez, Leonardo Zamora, Cristian Reyes-Martinez, Nicolas Salinas-Parra, Nicole Roldan, Catherina A Cuevas, Stefanny Figueroa, Alex Gonzalez-Vergara, Minolfa C Prieto
Recent studies suggested that activation of the PRR upregulates profibrotic markers through reactive oxygen species (ROS) formation; however, the exact mechanisms have not been investigated in CD cells. We hypothesized that activation of the PRR increases the expression of profibrotic markers through MAPK-dependent ROS formation in CD cells. Mouse renal CD cell line (M-1) was treated with recombinant prorenin plus ROS or MAPK inhibitors and PRR-shRNA to evaluate their effect on the expression of profibrotic markers...
July 11, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28695400/role-of-collecting-duct-renin-in-the-pathogenesis-of-hypertension
#4
REVIEW
Alexis A Gonzalez, Lucienne S Lara, Minolfa C Prieto
The presence of renin production by the principal cells of the collecting duct has opened new perspectives for the regulation of intrarenal angiotensin II (Ang II). Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are present in the tubular fluid coming from the proximal tubule and collecting duct. All the components needed for Ang II formation are present along the nephron, and much is known about the mechanisms regulating renin in juxtaglomerular cells (JG); however, those in the collecting duct remain unclear...
August 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28626074/a-type-potassium-channels-contribute-to-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#5
Soledad Pitra, Javier E Stern
Recent studies support an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic sympathetic and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We recently showed that PRR is expressed in VP neurons, and that their activation increases neuronal activity...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28624188/a-novel-single-strand-rnai-therapeutic-agent-targeting-the-pro-renin-receptor-suppresses-ocular-inflammation
#6
Atsuhiro Kanda, Erdal Tan Ishizuka, Atsushi Shibata, Takahiro Matsumoto, Hidekazu Toyofuku, Kousuke Noda, Kenichi Namba, Susumu Ishida
The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620832/the-pro-renin-receptor-and-its-interaction-partners
#7
REVIEW
Jörg Peters
The prorenin receptor was originally discovered as a receptor that binds renin and prorenin, thereby inducing pro-fibrotic intracellular signal cascades. These effects are partially mediated in vitro by angiotensin (ANG) and partially independent of ANG. Consequently, inhibitors of the interaction between the prorenin and the (pro)renin receptor (PRR) were designed hoping that they may prevent fibrotic tissue damage, for instance, in the kidney. However, this concept was challenged by the fact that overexpression of the PRR was not harmful at all, whereas depletion of the PRR was lethal or markedly detrimental...
June 15, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28619367/the-vasoprotective-axes-of-the-renin-angiotensin-system-physiological-relevance-and-therapeutic-implications-in-cardiovascular-hypertensive-and-kidney-diseases
#8
REVIEW
Xiao C Li, Jianfeng Zhang, Jia L Zhuo
The renin-angiotensin system (RAS) is undisputedly one of the most prominent endocrine (tissue-to-tissue), paracrine (cell-to-cell) and intracrine (intracellular/nuclear) vasoactive systems in the physiological regulation of neural, cardiovascular, blood pressure, and kidney function. The importance of the RAS in the development and pathogenesis of cardiovascular, hypertensive and kidney diseases has now been firmly established in clinical trials and practice using renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, type 1 (AT1) angiotensin II (ANG II) receptor blockers (ARBs), or aldosterone receptor antagonists as major therapeutic drugs...
June 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#9
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#10
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28465657/the-microrna-21-signaling-pathway-is-involved-in-prorenin-receptor-prr-induced-vegf-expression-in-arpe-19-cells-under-a-hyperglycemic-condition
#11
Rashidul Haque, P Michael Iuvone, Li He, Kimberly Su Chung Choi, Ashley Ngo, Samantha Gokhale, Madiha Aseem, Daniel Park
PURPOSE: MicroRNAs (miRNAs/miRs) are involved in a large number of biological functions and diseases, such as cancer, cardiovascular diseases, and diabetes. MiR-21 has been reported to target Sprouty homolog 1 (SPRY1), SMAD7, and PTEN. In this study, we examined the underlying role of miR-21 in the regulation of prorenin receptor (PRR)-mediated induction of vascular endothelial growth factor (VEGF) expression via targeting SMAD7, SPRY1, and PTEN in a hyperglycemic condition. METHODS: PRR-mediated induction of VEGF under a hyperglycemic condition (high glucose, 33mM) was studied by treating ARPE-19 cells with perindopril (10 µmol/l), which inhibits angiotensin II-mediated signaling...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28464775/renoprotection-by-direct-renin-inhibition-a-systematic-review-and-meta-analysis
#12
Nikolaos Louvis, James Coulson
Even mild abnormalities of the renal structure or function can increase the risk of mortality and complications in other organs. Therefore, safe and effective treatments are necessary in order to influence the progression of renal disease. We used 2 methods to assess the renoprotective effects of aliskiren: 1) a statistical analysis of clinical trials that investigated aliskiren-induced renoprotection, in terms of changes in serum creatinine concentration (sCr) or estimated glomerular filtration rate (eGFR), and, 2) clinical trials that investigated the renoprotective effects of aliskiren with respect to changes in albuminuria or proteinuria...
May 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28396529/brain-renin-angiotensin-system-does-it-exist
#13
COMPARATIVE STUDY
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...
June 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
#14
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
#15
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
#16
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...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28276504/pathologic-roles-of-receptor-associated-prorenin-system-in-idiopathic-epiretinal-membrane
#17
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
#18
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
#19
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
#20
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
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