Amelioration by beraprost sodium, a prostacyclin analogue, of established renal dysfunction in rat glomerulonephritis model

Yamada, Masahiro; Sasaki, Rie; Sato, Nahoko; Suzuki, Motohiro; Tamura, Mina; Matsushita, Teruo; Kurumatani, Hajimu

doi:10.1016/s0014-2999(02)01988-x

Cited by 26 publications

(31 citation statements)

References 23 publications

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“…37 Beraprost sodium has multiple effects directed to improve microcirculation, such as anti-platelet, vasolidator and antiinflammatory effects. 38 Taken together, the present results suggest that blood flow would be increased by vasodilator effect of human PGIS gene transfer, re-epithelialization would be promoted through the regeneration of epithelial cells by human HGF gene transfer, and finally, wound healing would be accelerated by the effects of human HGF and PGIS gene co-transfer in this model. These days, the numbers of patients suffering from incurable ulcers caused by diabetes mellitus or ischemic arterial diseases are increasing.…”

Section: Discussionsupporting

confidence: 64%

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

et al. 2006

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Section: Discussionsupporting

confidence: 64%

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

et al. 2006

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“…The anti-GBM GN rat is a model of human crescentic GN that rapidly progresses to renal failure. These rats are characterized by prominent inflammatory cell infiltration into the stroma, mesangial cell proliferation, crescent formation in the glomerulus, GBM thickening, and tubular dilatation (13,14). The renal function of these rats deteriorated progressively after the injection of anti-GBM serum, as reported (13,14).…”

Section: Resultsmentioning

confidence: 93%

Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis

Yamada

Katsuma²,

Adachi³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Glomerulonephritis (GN) is a progressive inflammation that may be caused by a variety of underlying disorders. It is the primary cause of chronic renal failure and end-stage renal disease, which require dialysis and transplantation worldwide. Immunosuppressive therapy has been used to treat GN clinically, but this treatment has had insufficient therapeutic effects. Here, we show that protein kinase CK2 is a key molecule in the progression of GN. cDNA microarray analysis identified CK2␣, the catalytic subunit of CK2, as a GNrelated, differentially expressed gene. Overexpression of CK2␣ was noted in the proliferative glomerular lesions in rat GN models and in renal biopsy specimens from lupus nephritis or IgA nephropathy patients. Administration of either antisense oligodeoxynucleotide against CK2␣ or low molecular weight CK2-specific inhibitors effectively prevented the progression of renal pathology in the rat GN models. The resolution of GN by CK2 inhibition may result from its suppression of extracellular signal-regulated kinase-mediated cell proliferation, and its suppression of inflammatory and fibrotic processes that are enhanced in GN. Our results show that CK2 plays a critical role in the progression of immunogenic renal injury, and therefore, CK2 is a potential target for GN therapy.antisense oligodeoxynucleotide ͉ microarray ͉ pharmacology G lomerulonephritis (GN) is a disease characterized by renal inflammation, causing destruction of glomeruli and adjacent structures, as well as loss of renal function. It is associated with conditions such as hematuria and proteinuria. Current treatment is still limited to supportive therapy, with or without nonspecific immunosuppressive drugs (1-3). Early cellular proliferation followed by subsequent fibrosis is a prominent hallmark of proliferative GN, and it may ultimately lead to end-stage renal disease (4). The involvement of extracellular stimuli, such as growth factors, cytokines, activated complement, and immune complexes in the pathogenesis of experimental and human GN has been known for many years. However, only recently have the intracellular mediators that transduce signals from noxious extracellular stimuli to unfettered cellular proliferation and accompanying excess extracellular matrix deposition begun to be unraveled (5). Experiments with cultured glomerular cells and certain animal models of experimental GN implicate the activation of extracellular signal-regulated kinase (ERK), which results in glomerular cellular proliferation (6).Protein kinase CK2 (formerly known as casein kinase II) is an extremely well conserved pleiotropic protein kinase with a growing list of Ͼ300 substrates, the majority of which are proteins implicated in signal transduction, gene expression, and transcription-related functions (7-11). Protein kinase CK2 is a ubiquitous heterotetrameric serine͞threonine protein kinase made up of two ␣ or ␣Ј catalytic subunits and two ␤-regulatory subunits. CK2 is activated during cell division, cellular differentiation, and embryogenesis, an...

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“…The transcription of mRNA for MCP-1, transforming growth factor-␤1 (TGF-␤1), IL-1␤ (IL-1␤), and TNF-␣ was evaluated by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) as previously described. 15,16 Transcription of endothelial nitric oxide synthase (eNOS) mRNA was evaluated as previously described, 17 with minor modifications (our cycle conditions: 38 cycles, 94°C for 30 seconds, 55°C for 30 seconds, and 72°C for 1 minute). The RT-PCR products were separated on 1.5% agarose gel and visualized by staining with ethidium bromide.…”

Section: Sironi Et Al Protective Effects Of Rosuvastatin In Shrsp 599mentioning

confidence: 99%

Rosuvastatin, but not Simvastatin, Provides End-Organ Protection in Stroke-Prone Rats by Antiinflammatory Effects

Sironi

Gianazza

Gelosa

et al. 2005

ATVB

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Objective-Brain abnormalities, preceded by a systemic inflammation, develop in spontaneously hypertensive stroke-prone rats (SHRSP). In this model, we investigated whether the hydrophilic statin, rosuvastatin, influences the development of inflammation associated with brain abnormalities. Because differences in hydrophilicity/hydrophobicity contribute to the differences in statin pharmacology, we also evaluated the effects of simvastatin, a lipophilic molecule Methods and Results-SHRSP, fed a high-salt diet, were treated long-term with vehicle or rosuvastatin (1 and 10 mg/kg per day). Brain abnormalities developed after 40Ϯ5 days and after 60Ϯ5 days of salt loading, in vehicle-treated and in rosuvastatin-treated (1 mg/kg per day) SHRSP, respectively. After 100 days of treatment, no damage was detectable in 30% of the rats treated with the highest dose of the drug. In comparison with vehicle-treated SHRSP, rosuvastatin treatment attenuated the transcription of monocyte chemoattractant protein-1, transforming growth factor-␤1, IL-1␤, and tumor necrosis factor-␣ in the kidney, and of P-selectin in brain vessels and increased the transcription of endothelial nitric oxide synthase mRNA in the aorta. Urinary excretion of acute-phase proteins increased with time in vehicle-treated animals but remained negligible in drug-treated animals. These effects are independent of changes in physiological parameters. Treatment of SHRSP with simvastatin (2 to 20 mg/kg per day) did not exert any protective effect. Key Words: inflammation Ⅲ statins Ⅲ rats Ⅲ brain ischemia Ⅲ proteome Ⅲ rosuvastatin Ⅲ simvastatin Ⅲ stroke-prone rats I nflammatory processes accompany tissue injury no matter what organ is involved. Data suggest that inflammation predisposes to ischemic vascular disease in general and to stroke in particular, because patients with chronic inflammatory disorders or with chronic or acute infection are at high risk for stroke. 1 High blood levels of inflammatory markers are associated with increased cardiovascular risk in healthy populations and in patients with coronary heart disease and ischemic stroke. 2 Moreover, in patients with an acute ischemic neurological event, a strong inflammatory response at the time of admission is associated with a less favorable outcome. 3 The inflammatory reaction therefore presents an attractive pharmacological opportunity for novel approaches in stroke. The spontaneously hypertensive stroke-prone rat (SHRSP) provides a useful tool to evaluate the contribution of inflammation to brain injury and to answer the question of whether antiinflammatory strategies may affect the genesis, progression, and outcome of brain damage. 4 We previously reported that SHRSP subjected to salt loading have an inflammatory condition characterized, before the appearance of brain damage, by the accumulation in plasma and urine of several acute-phase proteins (APP), including thiostatin, the most typical marker of an inflammatory response in the rat. 4 Serum and urine levels of this protein were found to be predic...

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Amelioration by beraprost sodium, a prostacyclin analogue, of established renal dysfunction in rat glomerulonephritis model

Cited by 26 publications

References 23 publications

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis

Rosuvastatin, but not Simvastatin, Provides End-Organ Protection in Stroke-Prone Rats by Antiinflammatory Effects

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