Decoupled syndecan 1 mRNA and protein expression is differentially regulated by angiotensin II in macrophages

Increased glomerular permeability to proteins is a characteristic feature of diabetic nephropathy (DN). The slit diaphragm is the major restriction site to protein filtration, and the loss of nephrin, a key component of the slit diaphragm, has been demonstrated in both human and experimental DN. Both systemic and glomerular hypertension are believed to be important in the pathogenesis of DN. Human immortalized podocytes were subjected to repeated stretch-relaxation cycles by mechanical deformation with the use of a stress unit (10% elongation, 60 cycles/min) in the presence or absence of candesartan (1 μM), PD-123319 (1 μM), and rosiglitazone (0.1 μM). Nephrin mRNA and protein expression were assessed using quantitative real-time PCR, immunoblotting, and immunofluorescence, and the protein expression of AT1 receptor and angiotensin II secretion were evaluated. Exposure to stretch induced a significant ∼50% decrease in both nephrin mRNA and protein expression. This effect was mediated by an angiotensin II-AT1 mechanism. Indeed, podocyte stretching induced both angiotensin II secretion and AT1 receptor overexpression, podocyte exposure to angiotensin II reduced nephrin protein expression, and both the AT-1 receptor antagonist candesartan and a specific anti-angiotensin II antibody completely abolished stretch-induced nephrin downregulation. Similar to candesartan, the peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, also inhibited stretch-induced nephrin downregulation, suggesting interference with stretch-induced activation of the angiotensin II-AT1 receptor system. Accordingly, rosiglitazone did not alter stretch-induced angiotensin II secretion, but it prevented AT1 upregulation in response to stretch. These results suggest a role for hemodynamic stress in loss of nephrin expression and allude to a role of PPAR-γ agonists in the prevention of this loss.

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Tanshinone IIA alters the transforming growth factor-β1/Smads pathway in angiotensin II-treated rat hepatic stellate cells

Journal of International Medical Research ◽

10.1177/0300060520926358 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052092635

Author(s):

Guo-wei Wei ◽

Ke-yue Li ◽

Ke-li Tang ◽

Cheng-Xian Shi

Keyword(s):

Angiotensin Ii ◽

Growth Factor ◽

Protein Expression ◽

Hepatic Stellate Cells ◽

Transforming Growth Factor ◽

Stellate Cells ◽

Transforming Growth Factor Β1 ◽

Tanshinone Iia ◽

Mrna And Protein Expression ◽

Tgf Β1

Objective To investigate the effects of tanshinone IIA on the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in angiotensin II-treated hepatic stellate cells (HSCs). Methods HSCs were cultured and treated with angiotensin II (10 μM) or angiotensin II (10 μM) plus tanshinone IIA (3, 10, or 30 μM). Cells were incubated for 48 hours and proliferation was determined with the Cell Counting Kit-8. The relative mRNA expression of TGF-β1, Smad4, and Smad7 was measured by quantitative real-time PCR, and the relative protein expression levels were investigated by western blotting. Results After angiotensin II treatment, cell proliferation was significantly accelerated. Furthermore, both the mRNA and protein expression of TGF-β1 and Smad4 was significantly up-regulated, while the mRNA and protein expression of Smad7 was significantly down-regulated compared with the control cells. Tanshinone IIA inhibited the observed effects of angiotensin II in a concentration-dependent manner, with significant inhibition exerted by tanshinone IIA at 10 and 30 μM. Conclusions Angiotensin II promotes the proliferation of HSCs, possibly by regulating the expression of components along the TGF-β1/Smads signaling pathway. Tanshinone IIA inhibits the angiotensin II-induced activation of this pathway, and may, therefore, have preventive and therapeutic effects in liver fibrosis.

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Collecting duct (pro)renin receptor targets ENaC to mediate angiotensin II-induced hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00178.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. F245-F253 ◽

Cited By ~ 31

Author(s):

Kexin Peng ◽

Xiaohan Lu ◽

Fei Wang ◽

Adam Nau ◽

Ren Chen ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Mrna Expression ◽

Collecting Duct ◽

Underlying Mechanism ◽

Ang Ii ◽

Induced Hypertension ◽

Mrna And Protein Expression ◽

Receptor Targets

The (pro)renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and the expression is further induced by angiotensin II (ANG II). The present study was conducted to investigate the role of CD PRR during ANG II-induced hypertension and to further explore the underlying mechanism. Radiotelemetry demonstrated that a 1-wk ANG II infusion gradually and significantly induced hypertensive response in floxed mice and this response was significantly attenuated in mice lacking PRR in the CD (termed CD PRR KO). ANG II infusion in floxed mice increased urinary renin activity and selectively induced renal medullary α-epithelial sodium channel (α-ENaC) mRNA and protein expression, all of which were blunted in the null mice. In cultured mpkCCD cells grown in Transwells, transepithelial Na+ transport as measured by using a volt-ohmmeter was transiently stimulated by acute ANG II treatment, which was abolished by a PRR antagonist, PRO20. In a chronic setting, ANG II treatment induced α-ENaC mRNA expression in mpkCCD cells, which was similarly blocked by PRO20. Chronic intramedullary infusion of an ENaC inhibitor amiloride in rats significantly attenuated ANG II-induced hypertension. Overall, the present study suggests that CD PRR contributes to ANG II-induced hypertension at least partially via activation of renal medullary ENaC.

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Glucose Promotes the Production of Interleukine-1β and Cyclooxygenase-2 in Mesangial Cells via Enhanced (Pro)Renin Receptor Expression

Endocrinology ◽

10.1210/en.2009-0442 ◽

2009 ◽

Vol 150 (12) ◽

pp. 5557-5565 ◽

Cited By ~ 59

Author(s):

Jiqian Huang ◽

Helmy M. Siragy

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Receptor Antagonist ◽

High Glucose ◽

Small Interfering Rna ◽

Mesangial Cells ◽

Receptor Blockade ◽

Mrna And Protein Expression ◽

Cox 2 ◽

Interfering Rna

Abstract (Pro)renin receptor (PRR) is present in renal glomeruli, and its expression is up-regulated in diabetes. Similarly, renal inflammation is increased in the presence of hyperglycemia. The linkage between PRR and renal inflammation is not well established. We hypothesized that glucose-induced up-regulation of PRR leads to increased production of the proinflammatory factors IL-1β and cyclooxygenase-2 (COX-2). Studies were conducted in rat mesangial cells (RMCs) exposed to 30 mmd-glucose for 2 wk followed by PRR small interfering RNA knockdown, IL-1 receptor blockade with IL-1 receptor antagonist or angiotensin II type 1 receptor blockade with valsartan. The results showed that d-glucose treatment up-regulates prorenin, renin, angiotensin II, PRR, IL-1β, and COX-2 mRNA and protein expression and increases phosphorylation of ERK1/2, c-Jun N-terminal kinase, c-Jun, and nuclear factor-κB (NF-κB) p65 (serine 276,468 and 536), respectively. PRR small interfering RNA attenuated PRR, IL-1β, and COX-2 mRNA and protein expressions and significantly decreased angiotensin II production and phosphorylation of ERK1/2 and NF-κB p65 associated with high glucose exposure. Similarly, IL-1 receptor antagonist significantly reduced COX-2 mRNA and protein expression induced by high glucose. COX-2 inhibition reduced high-glucose-induced PRR expression. We conclude that glucose induces the up-regulation of PRR and its ligands prorenin and renin, leading to increased IL-1β and COX-2 production via the angiotensin II-dependent pathway. It is also possible that PRR could enhance the production of these inflammatory cytokines through direct stimulation of ERK1/2-NF-κB signaling cascade.

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Enhanced angiotensin II-mediated central sympathoexcitation in streptozotocin-induced diabetes: role of superoxide anion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00246.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. R311-R320 ◽

Cited By ~ 19

Author(s):

Kaushik P. Patel ◽

William G. Mayhan ◽

Keshore R. Bidasee ◽

Hong Zheng

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Superoxide Anion ◽

Receptor Activation ◽

Diabetic Rats ◽

Type I ◽

Ang Ii ◽

Mrna And Protein Expression ◽

The Central Nervous System ◽

Streptozotocin Induced Diabetes

Studies have shown that the superoxide mechanism is involved in angiotensin II (ANG II) signaling in the central nervous system. We hypothesized that ANG II activates sympathetic outflow by stimulation of superoxide anion in the paraventricular nucleus (PVN) of streptozotocin (STZ)-induced diabetic rats. In α-chloralose- and urethane-anesthetized rats, microinjection of ANG II into the PVN (50, 100, and 200 pmol) produced dose-dependent increases in renal sympathetic nerve activity (RSNA), arterial pressure (AP), and heart rate (HR) in control and STZ-induced diabetic rats. There was a potentiation of the increase in RSNA (35.0 ± 5.0 vs. 23.0 ± 4.3%, P < 0.05), AP, and HR due to ANG II type I (AT1) receptor activation in diabetic rats compared with control rats. Blocking endogenous AT1 receptors within the PVN with AT1 receptor antagonist losartan produced significantly greater decreases in RSNA, AP, and HR in diabetic rats compared with control rats. Concomitantly, there were significant increases in mRNA and protein expression of AT1 receptor with increased superoxide levels and expression of NAD(P)H oxidase subunits p22phox, p47phox, and p67phox in the PVN of rats with diabetes. Pretreatment with losartan (10 mg·kg−1·day−1 in drinking water for 3 wk) significantly reduced protein expression of NAD(P)H oxidase subunits (p22phox and p47phox) in the PVN of diabetic rats. Pretreatment with adenoviral vector-mediated overexpression of human cytoplasmic superoxide dismutase (AdCuZnSOD) within the PVN attenuated the increased central responses to ANG II in diabetes (RSNA: 20.4 ± 0.7 vs. 27.7 ± 2.1%, n = 6, P < 0.05). These data support the concept that superoxide anion contributes to an enhanced ANG II-mediated signaling in the PVN involved with the exaggerated sympathoexcitation in diabetes.

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Age Determines the Magnitudes of Angiotensin II-Induced Contractions, mRNA, and Protein Expression of Angiotensin Type 1 Receptors in Rat Carotid Arteries

The Journals of Gerontology Series A ◽

10.1093/gerona/glt128 ◽

2013 ◽

Vol 69 (5) ◽

pp. 519-526 ◽

Cited By ~ 14

Author(s):

Z. Vamos ◽

P. Cseplo ◽

I. Ivic ◽

R. Matics ◽

J. Hamar ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Carotid Arteries ◽

Mrna And Protein Expression ◽

Angiotensin Type

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Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00148.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. H1279-H1287 ◽

Cited By ~ 31

Author(s):

Takashi Doi ◽

Tsuyoshi Sakoda ◽

Takafumi Akagami ◽

Toshio Naka ◽

Yoshitomo Mori ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Receptor Antagonist ◽

Myocardial Dysfunction ◽

Rho Kinase ◽

Ang Ii ◽

Rat Cardiomyocytes ◽

Endothelin 1 ◽

Ppar Agonists ◽

Mrna And Protein Expression

Aldosterone (Aldo) is recognized as an important risk factor for cardiovascular diseases. IL-18 induces myocardial hypertrophy, loss of contractility of cardiomyocytes, and apoptosis leading myocardial dysfunction. However, so far, there have been few reports concerning the interaction between Aldo and IL-18. The present study examined the effects and mechanisms of Aldo on IL-18 expression and the roles of peroxisome proliferator-activated receptor (PPAR) agonists in rat cardiomyocytes. We used cultured rat neonatal cardiomyocytes stimulated with Aldo to measure IL-18 mRNA and protein expression, Rho-kinase, and NF-κB activity. We also investigated the effects of PPAR agonists on these actions. Aldo, endothelin-1 (ET-1), and angiotensin II (ANG II) increased IL-18 mRNA and protein expression. Mineralocorticoid receptor antagonists, endothelin A receptor antagonist, and ANG II receptor antagonist inhibited Aldo-induced IL-18 expression. Aldo induced ET-1 and ANG II production in cultured media. Moreover, Rho/Rho-kinase inhibitor and statin inhibited Aldo-induced IL-18 expression. On the other hand, Aldo upregulated the activities of Rho-kinase and NF-κB. PPAR agonists attenuated the Aldo-induced IL-18 expression and NF-κB activity but not the Rho-kinase activity. Our findings indicate that Aldo induces IL-18 expression through a mechanism that involves, at a minimum, ET-1 and ANG II acting via the Rho/Rho-kinase and PPAR/NF-κB pathway. The induction of IL-18 in cardiomyocytes by Aldo, ET-1, and ANG II might, therefore, cause a deterioration of the cardiac function in an autocrine and paracrine fashion. The inhibition of the IL-18 expression by PPAR agonists might be one of the mechanisms whereby the beneficial cardiovascular effects are exerted.

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Effects of Angiotensin II on Erythropoietin Production in the Kidney and Liver

Molecules ◽

10.3390/molecules26175399 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5399

Author(s):

Yukiko Yasuoka ◽

Yuichiro Izumi ◽

Takashi Fukuyama ◽

Hideki Inoue ◽

Tomomi Oshima ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Renal Cortex ◽

The Body ◽

Outer Medulla ◽

Main Site ◽

Erythropoietin Production ◽

Collecting Ducts ◽

Mrna And Protein Expression

The kidney is a main site of erythropoietin production in the body. We developed a new method for the detection of Epo protein by deglycosylation-coupled Western blotting. Detection of deglycosylated Epo enables the examination of small changes in Epo production. Using this method, we investigated the effects of angiotensin II (ATII) on Epo production in the kidney. ATII stimulated the plasma Epo concentration; Epo, HIF2α, and PHD2 mRNA expression in nephron segments in the renal cortex and outer medulla; and Epo protein expression in the renal cortex. In situ hybridization and immunohistochemistry revealed that ATII stimulates Epo mRNA and protein expression not only in proximal tubules but also in collecting ducts, especially in intercalated cells. These data support the regulation of Epo production in the kidney by the renin–angiotensin–aldosterone system (RAS).

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Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-кB signaling pathways

AJP Renal Physiology ◽

10.1152/ajprenal.00350.2015 ◽

2016 ◽

Vol 310 (10) ◽

pp. F1103-F1112 ◽

Cited By ~ 14

Author(s):

Jia L. Zhuo ◽

H. Kobori ◽

Xiao C. Li ◽

R. Satou ◽

A. Katsurada ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Proximal Tubule ◽

Signaling Pathways ◽

Map Kinases ◽

Proximal Tubules ◽

Ang Ii ◽

Proximal Tubule Cells ◽

Mrna And Protein Expression ◽

Rats And Mice

Long-term angiotensin II (ANG II) infusion significantly increases ANG II levels in the kidney through two major mechanisms: AT1 receptor-mediated augmentation of angiotensinogen (AGT) expression and uptake of circulating ANG II by the proximal tubules. However, it is not known whether intracellular ANG II stimulates AGT expression in the proximal tubule. In the present study, we overexpressed an intracellular cyan fluorescent ANG II fusion protein (Ad-sglt2-ECFP/ANG II) selectively in the proximal tubule of rats and mice using the sodium and glucose cotransporter 2 (sglt2) promoter. AGT mRNA and protein expression in the renal cortex and 24-h urinary AGT excretion were determined 4 wk following overexpression of ECFP/ANG II in the proximal tubule. Systolic blood pressure was significantly increased with a small antinatriuretic effect in rats and mice with proximal tubule-selective expression of ECFP/ANG II ( P < 0.01). AGT mRNA and protein expression in the cortex were increased by >1.5-fold and 61 ± 16% ( P < 0.05), whereas urinary AGT excretion was increased from 48.7 ± 5.7 ( n = 13) to 102 ± 13.5 ( n = 13) ng/24 h ( P < 0.05). However, plasma AGT, renin activity, and ANG II levels remained unaltered by ECFP/ANG II. The increased AGT mRNA and protein expressions in the cortex by ECFP/ANG II were blocked in AT1a-knockout (KO) mice. Studies in cultured mouse proximal tubule cells demonstrated involvement of AT1a receptor/MAP kinases/NF-кB signaling pathways. These results indicate that intracellular ANG II stimulates AGT expression in the proximal tubules, leading to increased AGT formation and secretion into the tubular fluid, which contributes to ANG II-dependent hypertension.

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Modulation of steroidogenic enzymes by orphan nuclear transcriptional regulation may control diverse production of cortisol and androgens in the human adrenal

Journal of Endocrinology ◽

10.1677/joe.0.1810355 ◽

2004 ◽

Vol 181 (2) ◽

pp. 355-365 ◽

Cited By ~ 33

Author(s):

SN Kelly ◽

TJ McKenna ◽

LS Young

Keyword(s):

Transcriptional Regulation ◽

Angiotensin Ii ◽

Protein Expression ◽

Zona Glomerulosa ◽

Adrenal Androgen ◽

Adrenocortical Cells ◽

Steroid Production ◽

Response Element ◽

Steroidogenic Factor 1 ◽

Mrna And Protein Expression

The capacity of the adrenal to produce cortisol is controlled in part by 21-hydroxylase (CYP21) and the production of androgens by 17-hydroxylase/17-20-lyase (CYP17), in response to secretagogues including ACTH, angiotensin-II (A-II) and insulin. In this study we examined the capacity of human adrenocortical cells to produce cortisol and androgens in response to these secretagogues and their ability to regulate the expression of CYP21 and CYP17. In H-295 cells, forskolin and A-II were found to stimulate production of cortisol relative to androstenedione and a similar pattern of steroid production was noted in primary human adrenocortical cells. Both mRNA and protein expression of CYP21 was upregulated with forskolin and A-II alone and in combination, as detected by Northern and Western blotting. Whereas expression of CYP17 mRNA and protein was up regulated in the presence of forskolin and forskolin in combination with insulin. The ability of steroidogenic factor-1 (SF-1) and nur77 to regulate transcription of these enzymes was examined. Forskolin, A-II and insulin increased the protein expression of SF-1. Increased binding of SF-1 to its response element in the presence of forskolin, A-II and insulin was observed. Nur77 was expressed primarily in the zona glomerulosa and fasciculata. Increased protein expression of nur77 and the greatest binding of nur77 to its response element was seen when cells were stimulated with A-II in combination with forskolin. These data indicate that nur77 may preferentially regulate steroid enzyme genes relevant to cortisol production and thereby regulate differential cortisol and adrenal androgen production.

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