scholarly journals Renin gene expression in human kidney biopsies from patients with glomerulonephritis or graft rejection.

1995 ◽  
Vol 5 (7) ◽  
pp. 1469-1475
Author(s):  
J Wagner ◽  
S Volk ◽  
C C Haufe ◽  
A Ciechanowicz ◽  
M Paul ◽  
...  
Keyword(s):  
Gene Expression ◽  
Graft Rejection ◽  
Enzyme Inhibitor ◽  
Quantitative Polymerase Chain Reaction ◽  
Internal Standard ◽  
Human Kidney ◽  
Endogenous Gene ◽  
Tumor Nephrectomy ◽  
Renin Gene ◽  
Renin Mrna

The expression of renin mRNA was determined by a quantitative polymerase chain reaction assay in 27 human kidney samples: (1) 15 biopsies of patients with glomerulonephritis with or without angiotensin-converting enzyme inhibitor (ACEI) treatment; (2) biopsies of six renal allografts with graft rejection; and (3) six biopsy samples from unaffected parts of tumor nephrectomy specimens as controls. After isolation of RNA, 0.5 to 1 microgram of total RNA was used for reverse transcription to generate cDNA. The human renin gene was subsequently amplified by the use of two primers spanning the second and third exons. Renin expression was quantified with a renin cDNA mutant as the internal standard. It exhibited the same primer binding sites as the endogenous gene but carried a 155-basepair deletion, thus yielding a shorter amplification product. The number of glomeruli was counted by microscopic transillumination immediately after biopsy (median, 9 per biopsy; range, 2 to 23). Renin mRNA was expressed as femtograms of renin mRNA per glomerulus. Renin gene expression was lower in glomerulonephritic patients without ACEI treatment compared with that in control tumor nephrectomy samples, i.e., 63 +/- 20 (N = 7) versus 250 +/- 50 fg (N = 6) of renin mRNA/glomerulus, (P < 0.02), although plasma renin concentration in the glomerulonephritic patients was in the normal range. Significantly higher renin mRNA expression was found in glomerulonephritic patients treated with ACEI, i.e., 210 +/- 50 (N = 8) compared with 63 +/- 20 (N = 7) fg of renin mRNA/glomerulus in patient not treated with ACEI (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney

1993 ◽  
Vol 264 (4) ◽  
pp. R696-R702 ◽  
Author(s):  
A. Tufro-McReddie ◽  
R. L. Chevalier ◽  
A. D. Everett ◽  
R. A. Gomez
Keyword(s):  
Gene Expression ◽  
Aortic Coarctation ◽  
Perfusion Pressure ◽  
Receptor Gene ◽  
At1 Receptor ◽  
Northern Analysis ◽  
Renin Gene ◽  
Renin Mrna ◽  
Receptor Gene Expression

To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute hypoxia stimulates renin secretion and renin gene expression in vivo but not in vitro

1997 ◽  
Vol 272 (4) ◽  
pp. R1105-R1111 ◽  
Author(s):  
T. Ritthaler ◽  
K. Schricker ◽  
F. Kees ◽  
B. Kramer ◽  
A. Kurtz
Keyword(s):  
Gene Expression ◽  
Acute Hypoxia ◽  
Primary Cultures ◽  
Renin Secretion ◽  
Plasma Norepinephrine ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Renin Gene ◽  
Renin Mrna

This study aimed at examining the influence of acute hypoxia on renin secretion and renin gene expression in the kidney. To this end, male Sprague-Dawley rats were exposed to severe hypoxic stress (8% O2) or to carbon monoxide (0.1% CO) for 6 h, and plasma renin activity (PRA) and renal renin mRNA levels were determined. PRA values increased from 3 to 13 and 10 ng angiotensin I x h(-1) x ml(-1), and renin mRNA levels increased by 120 and 100% during hypoxia and CO, respectively. Lowering the PO2 from 150 to 20 or 7 mmHg in the gas atmosphere of primary cultures of renal juxtaglomerular cells had no influence on renin secretion and renin gene expression after 6 and 20 h. Our findings thus suggest that both arterial and venous hypoxia can be powerful stimulators of renin secretion and renin gene expression in vivo. Because renal denervation did not prevent stimulation of the renin system by hypoxia, the effect could be indirectly mediated via the baroreceptor-macula densa mechanism. Another potential mediator of the effect could be circulating catecholamines, since we found that plasma norepinephrine increased from 0.7 to 1.5 and 2.4 ng/ml and plasma epinephrine increased from 0.3 to 1.4 and 2.7 ng/ml during hypoxia and CO inhalation, respectively.

JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter

1999 ◽  
Vol 277 (4) ◽  
pp. F634-F642 ◽  
Author(s):  
Patrick L. Sinn ◽  
Xiaoji Zhang ◽  
Curt D. Sigmund
Keyword(s):  
Gene Expression ◽  
Systemic Circulation ◽  
Proximal Promoter ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Specific Expression ◽  
Renin Synthesis ◽  
Human Renin ◽  
Renin Gene ◽  
Renin Mrna ◽  
Cell Expression

In the kidney, renin gene expression is exquisitely localized to the juxtaglomerular (JG) cells lining the afferent arteriole, having the capacity to regulate renin synthesis in response to a variety of physiological cues. We investigated human renin gene expression in transgenic mice containing a genomic construct driven by 149 bp of its proximal promoter to elucidate whether this was sufficient to confer JG-specific expression. Whereas human renin mRNA was permissively expressed in most tissues, the transgene was expressed mainly in JG cells in the kidney. Active human renin and human prorenin were found in the systemic circulation at levels consistent with previous transgenic models. Remarkably, two lines displayed an appropriate upregulation of transgene mRNA in response to angiotensin-converting enzyme inhibition, and two lines exhibited a downregulation of transgene mRNA in response to subpressor and pressor doses of ANG II. Our results suggest that 149 bp of the human renin proximal promoter, in a context of a genomic construct, are sufficient to confer human renin expression in renal JG cells and at least some aspects of appropriate regulation.

Aldosterone enhances renin gene expression in juxtaglomerular cells

2004 ◽  
Vol 286 (2) ◽  
pp. F349-F355 ◽  
Author(s):  
Jürgen Klar ◽  
Helga Vitzthum ◽  
Armin Kurtz
Keyword(s):  
Gene Expression ◽  
Primary Cultures ◽  
Cellular Level ◽  
Juxtaglomerular Cells ◽  
Mrna Levels ◽  
Renin Synthesis ◽  
Corticosteroid Hormones ◽  
Renin Gene ◽  
Renin Mrna ◽  
Mrna Half Life

The secretion and synthesis of renin as the key regulator of the renin-angiotensin-aldosterone system are directly controlled by ANG II in the sense of a negative feedback. Because we found that renal afferent arterioles including the juxtaglomerular portion express the mineralocorticoid receptor, we aimed to characterize a possible direct effect of aldosterone on renin synthesis and renin secretion at the level of renal juxtaglomerular cells. Aldosterone (100 nM) clearly enhanced renin mRNA levels in primary cultures of mouse juxtaglomerular cells prestimulated with isoproterenol (100 nM) but had no effect on the exocytosis of stored renin. Similarly, in the mouse juxtaglomerular cell line As4.1, aldosterone time and concentration dependently increased renin mRNA abundance and prorenin secretion up to 2.5-fold. Moreover, aldosterone potentiated cAMP-induced renin gene expression in As4.1 cells. The effect of aldosterone was inhibited by spironolactone and was mimicked by corticosteroid hormones but not by sex steroids. Aldosterone had no influence on basal renin promoter activity but increased the renin mRNA half-life about threefold. In summary, these data suggest that aldosterone exerts a direct positive effect on renin gene expression at the cellular level probably by stabilizing renin mRNA.

Enhancement of Apoptosis-Related Gene Expression in Human Renal Graft Rejection

2000 ◽  
Vol 6 (S2) ◽  
pp. 626-627
Author(s):  
P. Y. Lau ◽  
J. Papadimitriou ◽  
C. Drachenberg ◽  
M. R. Weir ◽  
C. Wei
Keyword(s):  
Gene Expression ◽  
Kidney Transplantation ◽  
Graft Rejection ◽  
Human Kidney ◽  
Renal Tissue ◽  
Related Gene ◽  
Renal Graft ◽  
Normal Human ◽  
Apoptosis Related Gene ◽  
Renal Graft Rejection

Apoptosis or programmed cell death is involved in many diseases include end-stage renal failure. Apoptosis-related genes include both stimulate genes and inhibitory gene of apoptosis. The genes which stimulate apoptosis include p53 and p21-WAF. The genes which inhibit apoptosis include bcl-2 gene family. The mechanisms of apoptosis include p53-dependend pathway and p53- independent pathway. We hypothesized that apoptosis-related genes may activate in renal graft rejection after kidney transplantation. Therefore, the present study was designed to investigate apoptosis-related gene expression and localization by immunohistochemical staining (IHCS) in human renal tissues with graft rejection and compare with that in normal human renal tissue.Human renal biopsy (n=5) were obtained after kidney transplantation with mild and moderate renal rejection. Normal human kidney biopsy was obtained during nephrectomy. P53, p21-WAF and Bcl-2 levels in renal tissue were determined by IHCS. The results of IHCS was evaluated by IHCS staining density scores (0, no staining; 1, minimal staining; 2, mild staining; 3, moderate staining; and 4, strong staining).

Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life

1992 ◽  
Vol 262 (3) ◽  
pp. R459-R463 ◽  
Author(s):  
W. V. Page ◽  
S. Perlman ◽  
F. G. Smith ◽  
J. L. Segar ◽  
J. E. Robillard
Keyword(s):  
Gene Expression ◽  
Plasma Renin ◽  
Renal Nerves ◽  
Mrna Levels ◽  
Angiotensin I ◽  
Fetal Sheep ◽  
Close Analysis ◽  
Renin Gene ◽  
Renin Mrna

The role of renal nerves in regulating changes in plasma renin activity (PRA) and renal renin gene expression was studied in intact (n = 6) and denervated (n = 6) fetal sheep before birth and during the first 24 h after delivery. Renal denervation completely blunted the rise in PRA observed 24 h after delivery in newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys, predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than 0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of these results also revealed that renin mRNA levels were significantly higher (P less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3) than in newborn lambs delivered by cesarean section (n = 3). These results suggest that renal nerves play an important role in regulating renin gene expression and PRA during the transition from fetal to newborn life.

Replacement of connexin 40 by connexin 45 causes ectopic localization of renin-producing cells in the kidney but maintains in vivo control of renin gene expression

2009 ◽  
Vol 297 (2) ◽  
pp. F403-F409 ◽  
Author(s):  
Lisa Kurtz ◽  
Melanie Gerl ◽  
Wilhelm Kriz ◽  
Charlotte Wagner ◽  
Armin Kurtz
Keyword(s):  
Gene Expression ◽  
Wild Type ◽  
Renin Gene ◽  
Connexin 40 ◽  
Renin Mrna ◽  
The Media ◽  
Afferent Arterioles ◽  
Deficient Mice ◽  
Media Layer

Deletion of connexin 40 (Cx40) leads to ectopic hyperplasia of renin-producing cells in the kidney, which is associated with dysregulated hyperreninemia and hypertension. The aim of this study was to determine whether Cx45 is able to substitute the function of Cx40 with regard to the localization of renin-producing cells. For this purpose, we have studied the distribution of renin-expressing cells under both normal conditions and during a stimulatory challenge of the renin system by inducing salt deprivation in mice, achieved by replacing the coding sequence of the Cx40 gene with that of Cx45 (Cx40ki45). In both wild-type (WT) mice and Cx40ki45 mice under normal conditions, renin-expressing cells were located at the juxtaglomerular position, whereas in Cx40-deficient mice they were located in the periglomerular interstitium. Upon challenge of the renin system, renin mRNA and the number of renin-expressing cells increased in WT mice in the media layer of afferent arterioles, while neither parameter changed significantly in Cx40-deficient mice. In Cx40ki45 mice, challenge of the renin system markedly increased both renin mRNA and the number of renin-expressing cells. However, the newly recruited renin-expressing cells were localized mainly outside the afferent vessels in the periglomerular interstitium. We found no evidence of cell divisions in renin-expressing cells in any of the genotypes investigated in this study, suggesting that the ectopically localized, renin-expressing cells in Cx40ki45 mice were already preexisting but were not renin-expressing under normal conditions. In summary, we infer from our findings that the function of Cx40 for the localization of potential renin-producing cells cannot be substituted by that of Cx45, although the regulability of renin gene expression can.

Renin Gene Expression in Rat Tissues: A New Quantitative Assay Method for Rat Renin mRNA Using Synthetic cRNA

1988 ◽  
Vol 10 (2) ◽  
pp. 345-359 ◽  
Author(s):  
F. Suzuki ◽  
G. Ludwig ◽  
W. Hellmann ◽  
M. Paul ◽  
K. Lindpaintner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Assay ◽  
Assay Method ◽  
Rat Tissues ◽  
Renin Gene ◽  
Renin Mrna

scholarly journals Pressure-natriuresis and -diuresis in transgenic rats harboring both human renin and human angiotensinogen genes.

1998 ◽  
Vol 9 (12) ◽  
pp. 2212-2222
Author(s):  
B Dehmel ◽  
E Mervaala ◽  
A Lippoldt ◽  
V Gross ◽  
J Bohlender ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renin Angiotensin System ◽  
Renal Perfusion ◽  
Transgenic Rat ◽  
Water Excretion ◽  
Excretory Function ◽  
Human Renin ◽  
Renin Gene ◽  
Renin Mrna ◽  
Pressure Natriuresis

The hypertensive double transgenic rat harboring both the human renin and human angiotensinogen genes (dTGR) offers a unique opportunity to study the human renin-angiotensin system in an experimental animal model. Since nothing is known about the control of sodium and water excretion in these rats, this study was performed to compare pressure-natriuresis relationships in hypertensive dTGR and normotensive control rats harboring only the human renin gene (hREN), in order to determine how the pressure-natriuresis relationship is reset in hypertensive dTGR. To differentiate between extrinsic and intrinsic renal mechanisms, experiments were performed with and without renal denervation, and with and without infusions of vasopressin, norepinephrine, 17-OH-corticosterone, and aldosterone. Human and rat angiotensinogen and renin mRNA expression were also determined. In hREN without controlled renal function, urine flow and sodium excretion increased from 13 to 169 microl/min per g kidney wet weight (kwt) and from 1 to 30 micromol/min per g kwt, respectively, as renal perfusion pressure was increased from 67 to 135 mmHg. Renal blood flow (RBF) and GFR ranged between 3 to 7 and 0.9 to 1.5 ml/min per g kwt. In dTGR, pressure-natriuresis-diuresis relationships were shifted approximately 40 mmHg rightward. RBF was lower in dTGR than in hREN; GFR was not different. In dTGR with neurohormonal factors controlled, RBF was decreased and pressure-natriuresis-diuresis curves were not different compared to dTGR curves without these interventions. By light microscopy, the kidneys of these 6-wk-old dTGR and hREN rats were normal and indistinguishable. Both human and rat renin and angiotensinogen mRNA were expressed in the kidneys of dTGR. The two renin mRNA were decreased in dTGR, indicating a physiologic downregulation of renin gene expression by high BP. It is concluded that the renal pressure-natriuresis mechanism is reset toward higher pressure levels in dTGR and participates in the maintenance of hypertension. The reduced excretory function in dTGR depends on hREN and human angiotensinogen gene expression and is intrinsic to the kidney as opposed to extrarenal regulators.

Angiotensin II regulates renin gene expression

1990 ◽  
Vol 259 (6) ◽  
pp. F882-F887 ◽  
Author(s):  
D. W. Johns ◽  
M. J. Peach ◽  
R. A. Gomez ◽  
T. Inagami ◽  
R. M. Carey
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Messenger Rna ◽  
Specific Activity ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Osmotic Minipump ◽  
Renin Gene ◽  
Renin Mrna ◽  
Enalapril Treatment

We investigated the effect of angiotensin II (ANG II) and enalapril on accumulation of renin messenger RNA (mRNA) and on renal renin distribution (immunohistochemical analysis). Adult Wistar-Kyoto rats received enalapril (0.2 mg/ml) in distilled drinking water for 8 or 12 days. On day 5 of enalapril treatment, an osmotic minipump was implanted in the peritoneum that caused sustained release of ANG II (200 ng.kg-1.min-1) or vehicle (bovine serum albumin) for 3 or 7 days. Control rats received water for 8 or 12 days and osmotic minipump implantation (containing vehicle solution) on the 5th day. Renin mRNA was identified by hybridization with a 32P-labeled full-length complementary DNA and was detected by autoradiography. Enalapril treatment increased renal renin mRNA specific activity (renin mRNA/total RNA). Subsequent infusion of angiotensin II for 3 or 7 days decreased renal renin mRNA specific activity. In addition, renin immunostaining increased along the afferent arteriole after enalapril treatment; however, enalapril-induced spread of renin immunostaining was not inhibited by ANG II. Thus ANG II attenuates the accumulation of renin mRNA stimulated by enalapril treatment without alteration of renal renin distribution. The lack of effect of ANG II on renal renin distribution may be due to the length of turnover time for stored protein. These findings suggest the shortloop negative feedback of ANG II on renin reflects inhibition of renin synthesis by ANG II. Therefore, we propose that ANG II exerts a direct inhibitory effect on renin by regulation of renin gene expression in renal vasculature.

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