SMP-534 ameliorates progression of glomerular fibrosis and urinary albumin in diabetic<i>db/db</i>mice

Sugaru, Eiji; Nakagawa, Tsutomu; Ono-Kishino, Michiko; Nagamine, Jun; Tokunaga, Teruhisa; Kitoh, Makoto; Hume, W. Ewan; Nagata, Ryu; Taiji, Mutsuo

doi:10.1152/ajprenal.00357.2005

Cited by 27 publications

(30 citation statements)

References 43 publications

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“…Similarly, the Ccr data were inconclusive, although these levels in uninephrectomized db/db or db/m mice were significantly higher than those in db/m mice without uninephrectomy. These results are consistent with reports by other groups 35,36 and may still reflect hyperfiltration, an early symptom of diabetic nephropathy.…”

Section: Discussionsupporting

confidence: 93%

“…The Ccr levels of db/db mice are usually higher than those of db/m mice. 35 With uninephrectomy, the Ccr levels in either db/m or db/db mice are significantly increased as compared with those of db/m mice with two kidneys. 35 After 20 wk of sustained hyperglycemia and renal hyperfiltration, kidneys from untreated unine- Figure 5.…”

Section: Discussionmentioning

confidence: 89%

“…35 With uninephrectomy, the Ccr levels in either db/m or db/db mice are significantly increased as compared with those of db/m mice with two kidneys. 35 After 20 wk of sustained hyperglycemia and renal hyperfiltration, kidneys from untreated unine- Figure 5. Effect of PAI-1R on glomerular matrix protein accumulation in diabetic db/db mice from weeks 20 to 22.…”

Section: Discussionmentioning

confidence: 89%

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A PAI-1 Mutant, PAI-1R, Slows Progression of Diabetic Nephropathy

Huang

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et al. 2008

Journal of the American Society of Nephrology

109

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Plasminogen activator inhibitor-1 (PAI-1) has been implicated in renal fibrosis. In vitro, PAI-1 inhibits plasmin generation, and this decreases mesangial extracellular matrix turnover. PAI-1R, a mutant PAI-1, increases glomerular plasmin generation, reverses PAI-1 inhibition of matrix degradation, and reduces disease in experimental glomerulonephritis. This study sought to determine whether short-term administration of PAI-1R could slow the progression of glomerulosclerosis in the db/db mouse, a model of type 2 diabetes in which mesangial matrix accumulation is evident by 20 wk of age. Untreated uninephrectomized db/db mice developed progressive albuminuria and mesangial matrix expansion between weeks 20 and 22, associated with increased renal mRNA encoding ␣1(I) and (IV) collagens and fibronectin. Treatment with PAI-1R prevented these changes without affecting body weight, blood glucose, glycosylated hemoglobin, creatinine, or creatinine clearance; therefore, PAI-1R may prevent progression of glomerulosclerosis in type 2 diabetes.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 89%

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A PAI-1 Mutant, PAI-1R, Slows Progression of Diabetic Nephropathy

Huang

Border

et al. 2008

Journal of the American Society of Nephrology

109

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“…Additionally, we have studied whether SMP-534 has beneficial effects on renal fibrosis. We have shown that treatment with SMP-534 inhibits accumulation of ECM in kidney of diabetic db/db mouse or 5/6 nephrectomized rats and ameliorates renal function (13,15). In the present study, we investigated whether SMP-534 has beneficial effects on pulmonary fibrosis in bleomycin-treated hamsters.…”

mentioning

confidence: 89%

The anti-fibrotic agent SMP-534 attenuates bleomycin-induced pulmonary fibrosis in hamsters

Tsujimura¹,

Ono-Kishino²,

Nagamine³

et al. 2009

Biomed. Res.

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Pulmonary fibrosis is a progressive and lethal lung disease characterized by accumulation of ECM and loss of pulmonary function. However, no cure exists for this disease, and current treatments often fail to slow its progression or relieve its symptoms. We have previously reported that the anti-fibrotic agent SMP-534 has beneficial effects on renal fibrosis in animal model of nephropathy. In this study, we examined whether SMP-534 has beneficial effects on pulmonary fibrosis in bleomycin-treated hamsters. Treatment with SMP-534 [low dose (70 mg/kg) or high dose (110 mg/kg)] counteracted inhibition of body weight increase induced by bleomycin. In addition, SMP-534 significantly inhibited bleomycin-induced increase in lung hydroxyproline level, an index of collagen formation. Moreover, SMP-534 significantly ameliorated histological pulmonary fibrotic changes induced by bleomycin. The results of this study indicate that the anti-fibrotic agent SMP-534 may offer a new therapeutic option for the treatment of pulmonary fibrosis.

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“…Several AGE inhibitors also decrease TGF-levels. (Turgut F,2010, Sugaru E., 2006) CTGF Inhibitors -Connective tissue growth factor (CTGF/CCN2) has been associated with fibrosis in various tissues including the kidney. It is up-regulated in most models of DN.…”

Section: Antifibrotic Agents and Growth Factor Inhibitorsmentioning

confidence: 99%