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Prorenin receptor

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...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
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
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
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
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
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
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
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
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
Naro Ohashi, Shinsuke Isobe, Sayaka Ishigaki, Takahisa Suzuki, Takamasa Iwakura, Masafumi Ono, Tomoyuki Fujikura, Takayuki Tsuji, Atsushi Otsuka, Yasuo Ishii, Hiroshi Furuse, Akihiko Kato, Seiichiro Ozono, Hideo Yasuda
BACKGROUND: (Pro)renin receptor [(P)RR], a specific receptor for renin and prorenin, was identified as a member of the renin-angiotensin system (RAS). (P)RR is cleaved by furin, and soluble (P)RR [s(P)RR] is secreted into the extracellular space. Previous reports have indicated that plasma s(P)RR levels show a significant positive relationship with urinary protein levels, which represent renal damage. However, it is not fully known whether plasma s(P)RR reflects renal damage. METHODS: We recruited 25 patients who were admitted to our hospital to undergo heminephrectomy...
2016: PloS One
Hye Eun Yoon, Eun Nim Kim, Min Young Kim, Ji Hee Lim, In-Ae Jang, Tae Hyun Ban, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, Bum Soon Choi
Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice...
2016: Oxidative Medicine and Cellular Longevity
Ihor V Yosypiv
Prorenin receptor (PRR), a receptor for renin and prorenin and an accessory subunit of the vacuolar proton pump H(+)-ATPase, is expressed in the developing kidney. Global loss of PRR is lethal in mice, and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. With the advent of modern gene targeting techniques, including conditional knockout approaches, several recent studies have demonstrated critical roles for the PRR in several lineages of the developing kidney...
May 9, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Yun Liu, Sujun Zuo, Xiaoyan Li, Jinjin Fan, Xueqin Cao, Xueqing Yu, Qiongqiong Yang
To investigate the levels of (Pro) renin receptor [(P) RR], α-smooth muscle actin (α-SMA), fibronectin (FN), and vacuolar H(+)-ATPase (V-ATPase) subunits (B2, E, and c) in rat unilateral ureteral obstruction (UUO) models and rat proximal tubular epithelial cells (NRK-52E) treated with prorenin to elucidate the role of V-ATPase in these processes by activating the (P) RR. UUO significantly upregulated (P) RR, V-ATPase subunits, α-SMA and FN expression in tubulointerstitium or tubular epithelial cells. A marked colocalization of (P) RR and the B2 subunit was also observed...
2016: Scientific Reports
Quanbin Xu, Dane D Jensen, Hua Peng, Yumei Feng
The systemic renin-angiotensin system (RAS) has long been recognized as a critically important system in blood pressure (BP) regulation. However, extensive evidence has shown that a majority of RAS components are also present in many tissues and play indispensable roles in BP regulation. Here, we review evidence that RAS components, notably including the newly identified (pro)renin receptor (PRR), are present in the brain and are essential for the central regulation of BP. Binding of the PRR to its ligand, prorenin or renin, increases BP and promotes progression of cardiovascular diseases in an angiotensin II-dependent and -independent manner, establishing the PRR a promising antihypertensive drug target...
August 2016: Pharmacology & Therapeutics
Boye L Jensen
No abstract text is available yet for this article.
October 2016: Journal of the American Society of Nephrology: JASN
Tsuguo Nishijima, Kazuki Tajima, Yoshihiro Yamashiro, Keisuke Hosokawa, Akira Suwabe, Kazuhiro Takahashi, Shigeru Sakurai
(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients...
2016: Tohoku Journal of Experimental Medicine
Ellen F Carney
No abstract text is available yet for this article.
June 2016: Nature Reviews. Nephrology
Andressa Minussi Pereira Dau, Eduardo Pradebon da Silva, Paulo Roberto Antunes da Rosa, Felipe Tusi Bastiani, Karina Gutierrez, Gustavo Freitas Ilha, Fabio Vasconcellos Comim, Paulo Bayard Dias Gonçalves
The discovery of a receptor that binds prorenin and renin in human endothelial and mesangial cells highlights the possible effect of renin-independent prorenin in the resumption of meiosis in oocytes that was postulated in the 1980s.This study aimed to identify the (pro)renin receptor in the ovary and to assess the effect of prorenin on meiotic resumption. The (pro)renin receptor protein was detected in bovine cumulus-oocyte complexes, theca cells, granulosa cells, and in the corpus luteum. Abundant (pro)renin receptor messenger ribonucleic acid (mRNA) was detected in the oocytes and cumulus cells, while prorenin mRNA was identified in the cumulus cells only...
July 2016: Peptides
Nirupama Ramkumar, Deborah Stuart, Elena Mironova, Vladislav Bugay, Shuping Wang, Nikita Abraham, Atsuhiro Ichihara, James D Stockand, Donald E Kohan
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 mo 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 investigated the signaling mechanisms by which PRR regulates Na(+) balance...
July 1, 2016: American Journal of Physiology. Renal Physiology
Nirupama Ramkumar, Donald E Kohan
Recent evidence suggests that the renal tubular renin angiotensin system regulates urinary Na(+) and water excretion and blood pressure. Three key components of the tubular renin angiotensin system, namely renin, prorenin receptor, and angiotensin-II type 1 receptor, are localized to the collecting duct. This system may modulate collecting duct Na(+) and water reabsorption via angiotensin-II-dependent and angiotensin-II-independent pathways. Further, the system may be of greatest relevance in hypertensive states and particularly those characterized by high circulating angiotensin-II...
April 2016: Current Hypertension Reports
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