Angiotensin II type I receptor blockade suppresses glomerular renin-angiotensin system activation, oxidative stress, and progressive glomerular injury in rat anti-glomerular basement membrane glomerulonephritis

Kinoshita, Yukiko; Kondo, Shuji; Urushihara, Maki; Suga, Kenichi; Matsuura, Sato; Takamatsu, Masanori; Shimizu, Masaru; Nishiyama, Akira; Kawachi, Hiroshi; Kubo, Shoji

doi:10.1016/j.trsl.2011.05.003

Cited by 29 publications

(17 citation statements)

References 38 publications

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“…For example, there is evidence of marked oxidative stress in nephrotoxic serum models of mouse glomerulonephritis, and in particular marked upregulation of NADPH oxidase and increased generation of superoxide free radicals (Kinoshita et al, 2011). Interestingly, these effects were reduced by AT 1 antagonists, which have long been known to reduce histopathologic changes and proteinuria in this model (Suzuki et al, 1998;Mii et al, 2009;Aki et al, 2010).…”

Section: Discussionmentioning

confidence: 80%

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

Abkhezr

Dryer

2014

Mol Pharmacol

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Previous studies have shown that the transcription factor signal transducer and activator of transcription-3 (STAT3) in podocytes plays an important role in progression of HIV nephropathy and in collapsing forms of glomerulonephritis. Here, we have observed that application of 100 nM angiotensin II (Ang II) to cultured podocytes for 6-24 hours causes a marked increase in the phosphorylation of STAT3 on tyrosine Y705 but has no effect on phosphorylation at serine S727. By contrast, Ang II treatment of short periods (20-60 minutes) caused a small but consistent suppression of tyrosine phosphylation of STAT3. A similar biphasic effect was seen after treatment with the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG), an agent that causes activation of Ca -calmodulin-dependent protein kinase II. The stimulatory effects of Ang II appear to be mediated by secretion and accumulation of an unknown factor into the surrounding medium, as they are no longer detected when medium is replaced every 2 hours even if Ang II is continuously present. By contrast, the inhibitory effect of Ang II on STAT3 phosphorylation persists with frequent medium changes. Experiments with neutralizing and inhibitory antibodies suggest that the STAT3 stimulatory factor secreted from podocytes is not interleukin-6, but also suggest that this factor exerts its actions through a receptor system that requires glycoprotein 130.

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Section: Discussionmentioning

confidence: 80%

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

Abkhezr

Dryer

2014

Mol Pharmacol

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“…To investigate whether local RAS activation and pathological glomerular alterations occur in nephritic glomeruli with crescent formation, we studied the effects of ARB on rat anti-GBM antibody-induced GN [38]. Treatment with ARB improved proteinuria and pathological alterations, such as crescent formation and glomerulosclerosis, and had a significant inhibitory effect on the enhanced expression of AGT, Ang II, and AT1 receptor, as well as superoxide production and glomerular α-smooth muscle action.…”

Section: Glomerulonephritismentioning

confidence: 99%

“…Moreover, the concentrations of Ang II and TGF-β1 in the supernatant of cultured glomeruli were significantly enhanced in vehicle-treated nephritic rats, whereas the production of these compounds was significantly inhibited in ARB-treated rats. These findings indicate that increased glomerular RAS activity and the resulting increase in Ang II production play important roles in progressive glomerular injury by inducing oxidative stress and TGF-β1 expression [38]. Monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of crescentic GN and is presumed to be a key mediator of chemotaxis and macrophage activation [37].…”

Section: Glomerulonephritismentioning

confidence: 99%

Role of the intrarenal renin–angiotensin system in the progression of renal disease

Urushihara

Kubo

2016

Pediatr Nephrol

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The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

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“…33 Phlogogenic cells can release enzymes that generate Ang II, including ACE in monocytes/ macrophages 34,35 and cathepsin G from neutrophils. 36 The local accumulation of Ang II activates AT 1 receptors in different cell types further sustaining the inflammatory environment via the production of reactive oxygen species, cytokines, and adhesion molecules.…”

Section: Progenitor Cell and Hyperplastic Lesionmentioning

confidence: 99%

Nature and Mediators of Parietal Epithelial Cell Activation in Glomerulonephritides of Human and Rat

Rizzo

Perico

Gagliardini

et al. 2013

The American Journal of Pathology

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Bowman's capsule parietal epithelial cell activation occurs in several human proliferative glomerulonephritides. The cellular composition of the resulting hyperplastic lesions is controversial, although a population of CD133(+)CD24(+) progenitor cells has been proposed to be a major constituent. Mediator(s) involved in proliferation and migration of progenitor cells into the Bowman's space have been poorly explored. In a series of 36 renal biopsies of patients with proliferative and nonproliferative glomerulopathies, dysregulated CD133(+)CD24(+) progenitor cells of the Bowman's capsule invade the glomerular tuft exclusively in proliferative disorders. Up-regulation of the CXCR4 chemokine receptor on progenitor cells was accompanied by high expression of its ligand, SDF-1, in podocytes. Parietal epithelial cell proliferation might be sustained by increased expression of the angiotensin II (Ang II) type-1 (AT1) receptor. Similar changes of CXCR4, SDF-1, and AT1 receptor expression were found in Munich Wistar Frömter rats with proliferative glomerulonephritis. Moreover, an angiotensin-converting enzyme inhibitor normalized CXCR4 and AT1 receptor expression on progenitors concomitant with regression of crescentic lesions in a patient with crescentic glomerulonephritis. These results suggest that glomerular hyperplastic lesions derive from the proliferation and migration of renal progenitors in response to injured podocytes. The Ang II/AT1 receptor pathway may participate, together with SDF-1/CXCR4 axis, to the dysregulated response of renal precursors. Thus, targeting the Ang II/AT1 receptor/CXCR4 pathways may be beneficial in severe forms of glomerular proliferative disorders.

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Angiotensin II type I receptor blockade suppresses glomerular renin-angiotensin system activation, oxidative stress, and progressive glomerular injury in rat anti-glomerular basement membrane glomerulonephritis

Cited by 29 publications

References 38 publications

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

Role of the intrarenal renin–angiotensin system in the progression of renal disease

Nature and Mediators of Parietal Epithelial Cell Activation in Glomerulonephritides of Human and Rat

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