Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced chronic glomerulosclerosis

Wang, Yingrui; Krämer, Stephanie; Loof, Tanja; Martini, Sebastian; Kron, Susanne; Kawachi, Hiroshi; Shimizu, Fuijo; Neumayer, Hans‐H.; Peters, Harm

doi:10.1111/j.1523-1755.2005.00380.x

Cited by 49 publications

(74 citation statements)

References 38 publications

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“…The mAb 1-22-3 antibody binds to a thy1-like antigen on the surface of mesangial cells of the kidney and causes a fast complement-dependent and NO-dependent mesangial cell lysis within the next 24 h (17,27). The progression in cGS is linked to the uninephrectomy that is performed before anti-thy1 antibody injection, since the glomerular disease resolves over ϳ4 wk in animals with two kidneys (17,21,27). Control animals were injected with equal volumes of PBS only.…”

Section: Methodsmentioning

confidence: 99%

“…Chronic-progressive glomerulosclerosis (cGS) was produced by surgically removing one kidney and intravenously injecting the monoclonal antibody mAb 1-22-3 (5 mg/kg body wt in PBS, pH ϭ 7.4) 3 days later (17,21,27). The mAb 1-22-3 antibody binds to a thy1-like antigen on the surface of mesangial cells of the kidney and causes a fast complement-dependent and NO-dependent mesangial cell lysis within the next 24 h (17,27). The progression in cGS is linked to the uninephrectomy that is performed before anti-thy1 antibody injection, since the glomerular disease resolves over ϳ4 wk in animals with two kidneys (17,21,27).…”

Section: Methodsmentioning

confidence: 99%

“…In this model, a single injection of a high dose of anti-thy1 antibody into uninephrectomized rats leads to a short-term complement-and nitric oxide-mediated acute glomerulonephritis, which then, over months, progresses autonomously toward persistent glomerulosclerosis, marked tubulointerstitial fibrosis, and renal insufficiency in a not primarily immune-mediated manner (17,21,27). This model has been termed anti-thy1-induced chronic glomerulosclerosis or anti-thy1-induced renal fibrosis (17,27). The course of experimental progressive anti-thy1-induced chronic glomerulosclerosis mimics to a relevant degree advancing mesangioproliferative nephropathy in humans and thus can act as an experimental model for studying human disease.…”

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confidence: 99%

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Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat

Krämer

Wang-Rosenke²,

Scholl³

et al. 2008

American Journal of Physiology-Renal Physiology

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-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat. Am J Physiol Renal Physiol 294: F440-F449, 2008. First published December 19, 2007 doi:10.1152/ajprenal.00379.2007.-Treatment options in human mesangioproliferative glomerulonephritis/sclerosis, mostly IgA nephropathy, are limited. Progressive mesangioproliferative nephropathy represents a major cause of end-stage kidney disease. The present study explores the efficacy of low-dose mTOR inhibition by rapamycin in a chronic-progressive model of mesangioproliferative glomerulosclerosis (cGS). cGS was induced by high-dose anti-thy1 antibody injection into uninephrectomized rats. Rapamycin administration (2.5 mg ⅐ kg Ϫ1 ⅐ body wt Ϫ1 ) was started 10 days after antibody injection and continued until week 20. cGS was characterized by advancing proteinuria, increased blood pressure, marked tubulointerstitial and glomerular fibrosis, cell proliferation and round cell infiltration, and impaired renal function. KruskalWallis and Mann-Whitney U-tests were used for statistical analysis. The course of chronic anti-thy1-induced glomerulosclerosis was significantly attenuated by low-dose rapamycin treatment. In week 20, this was demonstrated by improvements in proteinuria (Ϫ38%), systolic blood pressure (Ϫ16 mmHg), tubulointerstitial and glomerular histological matrix accumulation (Ϫ61 and Ϫ24%), transforming growth factor-␤1 overexpression (Ϫ41 and Ϫ47%), collagen I deposition (Ϫ53 and Ϫ65%), cell proliferation (Ϫ90 and Ϫ76%), and leukocyte number (macrophages Ϫ52 and Ϫ53%; lymphocytes Ϫ58 and 51%), respectively. Rapamycin improved renal function as well (blood creatinine Ϫ0.68 mg/dl, urea Ϫ66.7 mg/day, and creatinine clearance ϩ0.13 ml ⅐ min Ϫ1

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat

Krämer

Wang-Rosenke²,

Scholl³

et al. 2008

American Journal of Physiology-Renal Physiology

Self Cite

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“…5,6 Recent pharmacologic studies suggested that soluble GC are involved in a chronic model of glomerulonephritis 7,8 ; however, little is known about the role of receptor GC in renal diseases.…”

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confidence: 99%

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G Ϫ/Ϫ mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G Ϫ/Ϫ mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-B were lower in GC-G Ϫ/Ϫ mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G Ϫ/Ϫ mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

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“…Several studies have shown that enhanced NO availability improves the clinical course of anti-Thy1-glomerulonephritis (17,28), presumably via stimulation of endothelial NO synthase (eNOS). Consistently, enhancement of NO-stimulated cGMP production by soluble guanylate cyclase slows progression of anti-Thy1-glomerulonephritis (32). Rosiglitazone has been shown to enhance NO production by increasing eNOS transcription in isolated endothelial cells and eNOS phosphorylation in mice hearts (6) and isolated endothelial cells (20).…”

Section: Ajp-renal Physiolmentioning

confidence: 81%

Amelioration of anti-Thy1-glomerulonephritis by PPAR-γ agonism without increase of endothelial progenitor cell homing

Westerweel¹,

Ouden²,

Nguyen³

et al. 2008

American Journal of Physiology-Renal Physiology

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Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced chronic glomerulosclerosis

Cited by 49 publications

References 38 publications

Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat

Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Amelioration of anti-Thy1-glomerulonephritis by PPAR-γ agonism without increase of endothelial progenitor cell homing

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