Disease relevance of REN

• Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma [1].
• We examined the role of two variations of the aldosterone synthase gene (CYP11B2), one located in the promoter of the gene, T-344C, the other in the 7th exon, the T4986C (Val/Ala), on plasma levels of renin and aldosterone, blood pressure, and arterial stiffness in subjects with essential hypertension [2].
• Genetic variability in the renin angiotensin system may modify renal responses to injury and disease progression [3].
• In a sample of 103 low renin hypertensive patients, 218 patients with primary aldosteronism, and 90 normotensive individuals, we found a high level of conversion of CYP11B genes and four cases of GSH caused by unequal crossing over but no gene conversions of the type expected to cause GSH [4].
• All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels [5].

Psychiatry related information on REN

• COX-2 expression increases in high renin states and in response to a high-sodium diet or water deprivation [6].
• On psychometric testing, patients with high-renin hypertension, but not those with normal plasma renin activity, exhibited suppressed hostility (P less than 0.01), a behavioral pattern linked to increased sympathetic activity [7].
• The renin response to psychological stress, in contrast to those of ACTH and prolactin, is not mediated by the bed nucleus of the stria terminalis and is not suppressed by benzodiazepine anxiolytics [8].
• Individual differences in blood-pressure between these two diets correlated closely with concomitant differences in plasma renin activity (r = 0.75) [9].
• This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development [10].

High impact information on REN

• The renin angiotensin aldosterone system has an important role antagonizing the vasodilatory cyclic GMP system [11].
• Moreover, adenosine tonically inhibits the renal release of renin and stimulates NaCl transport in the cortical proximal tubule but inhibits it in medullary segments including the medullary thick ascending limb [12].
• Recently, some of the in vivo targets and mechanisms leading to changes in neuronal adaptation, smooth muscle relaxation and growth, intestinal water secretion, bone growth, renin secretion, and other important functions have been identified [13].
• Morphology, physiology, and molecular biology of renin secretion [14].
• We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1 [15].

Chemical compound and disease context of REN

• Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1-14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death [1].
• In renovascular models of hypertension associated with a stimulated renin-angiotensin system (two-kidney, one-clip), blood pressure reduction by ACE inhibitors was attenuated by icatibant, whereas in rats with genetic hypertension with normal to low plasma renin, blood pressure reduction through ACE inhibitors was not affected [16].
• Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion [17].
• In 4-week-old dTGR, long-term treatment with ACE inhibition (cilazapril), AT1 receptor blockade (valsartan), and human renin inhibition (RO 65-7219) (each drug 10 mg/kg by gavage once a day for 3 weeks) completely prevented the development of albuminuria [18].
• Response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to long-term administration of captopril in patients with severe, treatment-resistant malignant hypertension [19].

Biological context of REN

• Production of renin is critically dependent on modulation of REN mRNA stability [20].
• Functionally, this cAMP-based mRNA stabilization is accompanied by a 3- to 6-fold upregulation of REN mRNA binding proteins [21].
• We previously reported that the presence of the human renin and systemically expressed hAGT transgene complemented the lethality observed in AGT-/- mice [22].
• Upon decreasing HADHB mRNA with RNA interference, renin protein and mRNA stability increased, whereas RNA interference against HuR caused these to decrease [20].
• Baroreflex sensitivity and variants of the renin angiotensin system genes [23].

Anatomical context of REN

• Human REN immunostaining was observed in the dorsal cochlear nucleus, hypothalamus, and cortex [24].
• Using human prorenin as a model, we show that PC1 can process it to active renin in cells containing secretory granules, such as the somatomammotroph cell line GH4, but not in cells which lack granules, such as the Chinese hamster ovary or African green monkey kidney epithelial (BSC-40) cell lines [25].
• Human PC5 was colocalized with renin by immunohistochemistry in the zona glomerulosa of the adrenal gland, suggesting that it could participate in the activation of a local renin-angiotensin system in the human adrenal cortex [26].
• Ectopic renin expression by cyst epithelium was first reported in 1992 (Torres VE, Donovan KA, Sicli G, Holley KE, Thibodeau ST, Carretero OA, Inagami T, McAteer JA, and Johnson CM. Kidney Int 42: 364-373, 1992) [27].
• Angiotensinogen (AGT) is mainly expressed in glial cells in close proximity to renin-expressing neurons in the brain [28].

Associations of REN with chemical compounds

• Renin (REN) requires seconds to convert angiotensinogen (AGT) to angiotensin I [29].
• Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques [30].
• To accomplish this, we produced mice that express human renin (hREN) under the control of the kidney androgen-regulated promoter (KAP), which is androgen responsive [31].
• Renin and aldosterone levels were evaluated by using a radioimmunoassay [2].
• The cAMP mechanisms that regulate renin mRNA target, at least in large part, other genes that presumably encode some of these proteins [32].

Physical interactions of REN

• RNase degradation assays confirm that 3'-UTR binding proteins are able to protect and stabilize REN mRNA in vitro [21].
• RnBP has been shown to bind and inactivate renin, a key player of the blood pressure regulating renin-angiotensin system [33].
• The M6P-R is a clearance receptor that binds exclusively the glycosylated forms of renin and prorenin [34].
• Angiotensin receptor antagonists inhibit the renin angiotensin system at different levels from ACE inhibitors by selectively blocking the binding of angiotensin II to AT1 receptors [35].
• Genetic and molecular properties of human and rat renin-binding proteins with reference to the function of the leucine zipper motif [36].

Enzymatic interactions of REN

• Previous studies have demonstrated that the mouse proprotein convertase PC1 (mPC1) accurately cleaves human prorenin to generate active renin and that this processing event appears to require co-packaging in secretory granules [37].
• Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA [38].

Regulatory relationships of REN

• Recombinant RnBP inhibited porcine renin activity in a dose dependent manner [39].
• As the renin gene is negatively regulated by calcium in the same way as the parathormone (PTH) gene, we hypothesized that a similar molecular transcriptional mechanism could be involved [40].
• The angiotensin II (Ang II) type 1 (AT1) receptor is highly expressed on juxtaglomerular (G) cells and is assumed to be involved in the negative short loop feedback regulation of renin secretion and in the suppression of Ang II-mediated JG cell proliferation and/or growth [41].
• These results suggest that intrarenal ANG II content can be regulated independently of renal renin content [42].
• BACKGROUND: Renin Angiotensin system is involved in renal function and its polymorphisms may influence diabetic nephropathy [43].

Other interactions of REN

• On the contrary, we show herein that the presence of the human renin and kidney-specific hAGT transgene cannot rescue lethality in AGT-/- mice [22].
• Immunohistochemistry demonstrated enrichment of HADHB in renin-producing renal juxtaglomerular cells [20].
• We have developed a new assay method for GlcNAc 2-epimerase activity using a system of N-acyl-D-hexosamine oxidase coupled with peroxidase and employed this method to study the effects of renin on GlcNAc 2-epimerase activity [44].
• We also revealed in the Ohasama Study that the Trp460 allele of ADD1 is associated with hypertension in young subjects with low renin activity [45].
• Immunohistochemistry results were as follows: vimentin (positive), renin (weakly positive), smooth muscle actin (focal immunoreactivity), and cytokeratin (negative) [46].
• When the human renin Pal3 site was replaced by the consensus PPRE sequence, PPARgamma knockdown abrogated the effect of rosiglitazone on renin promoter activity [47].

Analytical, diagnostic and therapeutic context of REN

• Measuring REN with direct radioimmunoassay or by enzyme kinetic assay gave similar results [29].
• Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT(2) and/or AT(1) mRNAs and proteins determined by RT-PCR and/or Western blotting, respectively [1].
• Renin can be detected in cardiovascular and other tissues but it disappears after bilateral nephrectomy indicating that tissues can take up or bind renal renin from the circulation [48].
• Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients [3].
• To identify hREN mRNA binding proteins, electrophoretic mobility shift assays, UV cross-linking and RNA-affinity chromatography with subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were performed [21].

References