Mindin: a novel marker for podocyte injury in diabetic nephropathy

Murakoshi, Maki; Tanimoto, Masuhisa; Gohda, Tomohito; Hagiwara, Shinji; Takagi, Miyuki; Horikoshi, Satoshi; Tomino, Yasuhiko

doi:10.1093/ndt/gfq708

Cited by 33 publications

(41 citation statements)

References 29 publications

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“…In this analysis, we focused on mindin (also called spondin 2, SPON2 ) as a possible biomarker for several reasons [30,31]. Mindin protein expression levels in the glomeruli of KK mice were significantly upregulated with the progression of DN, they were mainly localized in podocytes by immunohistochemical staining and were a secreted protein.…”

Section: New Biomarkersmentioning

confidence: 99%

The Prevalence and Management of Diabetic Nephropathy in Asia

Tomino

Gohda²

2015

Kidney Dis

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Background: Diabetic nephropathy (DN), especially type 2 diabetes, is now increasing rapidly worldwide, also in Asian countries, and is one of the major long-term vascular complications. The pathogenesis of DN involves both genetic and environmental factors. Around 30-40% of type 2 diabetic patients develop DN despite strict blood glucose and/or blood pressure control. Although it is considered that the genetic background may influence the initiation and progression of DN, the candidate genes are still obscure. Summary: To search for genes that are involved in the susceptibility of DN, a candidate gene approach was taken in the beginning before the development of genome-wide association studies. Although a candidate gene approach can detect rare genetic variants, in advance we need known or presumed pathophysiological knowledge of the specific gene. Investigations using spontaneous animal models are important to determine the pathogenesis and treatment of DN patients. There are many spontaneous animal models, such as the NOD and Akita mice for type 1 diabetes and the Ob/Ob, db/db, Tsumura Suzuki Obese Diabetics, and KK-A^y mice for type 2 diabetes. Furthermore, the toxicity of persistent hyperglycemia, the activation of reactive oxygen species, systemic and/or glomerular hypertension, microinflammation, dyslipidemia, and other factors are considered to play important roles. Diabetic patients with normoalbuminuria and normal renal function showed typical histological patterns of DN. The discovery of a specific and reliable diagnostic and prognostic biomarker other than albuminuria is urgently needed and indispensable. Since large clinical trials of oral hypoglycemic drugs in renal failure are lacking, these recommendations will need to be regularly updated after results of larger randomized trials with longer follow-up durations are available. Key Messages: It is necessary to summarize the basic and clinical features of DN patients in Asia and to use these for the treatment of such patients. Facts from East and West: The prevalence of DN is increasing in Asia and Western countries alike. The deletion (D) allele of the angiotensin-converting enzyme gene is associated with progression to end-stage renal disease in Asian patients with DN, but this association is uncertain in Europeans. An association between DN and polymorphism of the gene coding for acetyl coenzyme A carboxylase β has been reported in Asian and Western populations. Both in Japan and the US, criteria for diagnosis are a 5-year history of diabetes and persistent albuminuria. Renal biopsy should be done in patients with severe hematuria, cellular casts and - in the US - hepatitis and HIV to rule out other pathologies. Diabetic retinopathy is considered a key criterion in Japan, but the absence of it does not rule out DN in the US. Enlargement of the kidney is observed as a diagnostic criterion in Japan. The differential use of renal biopsy as diagnostic tool might account for a different prevalence between Asian countries. Some Japanese diabe...

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Section: New Biomarkersmentioning

confidence: 99%

The Prevalence and Management of Diabetic Nephropathy in Asia

Tomino

Gohda²

2015

Kidney Dis

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“…At the end of all these processes, increase in mesangial matrix, thickening of basement membrane and podocyte injury occur. Recent studies have indicated that podocyte injury is a hallmark of the mechanisms in the pathogenesis of glomerular disease and DN . Inflammatory and immune response mechanisms may also play a key role.…”

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confidence: 99%

Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic nephropathy

et al. 2015

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“…To answer these questions, we established KK/Ta mice expressing human adiponectin in the liver. The KK/Ta mouse is an animal model of metabolic syndrome exhibiting moderate obesity with excessive visceral fat accumulation, hyperinsulinemia, dyslipidemia and hyperglycemia (Liao et al 2003, Tanimoto et al 2004, Akagiri et al 2008, Murakoshi et al 2010. Here, we showed that hyperadiponectinemia prolonged the lifespan of this murine model of metabolic syndrome without affecting body weight by attenuating AKT signaling and chronic low-grade inflammation.…”

Section: Introductionmentioning

confidence: 61%

Hyperadiponectinemia protects against premature death in metabolic syndrome model mice by inhibiting AKT signaling and chronic inflammation

Otabe¹,

Wada²,

Hashinaga³

et al. 2012

Journal of Endocrinology

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We previously reported that transgenic (Tg) expression of adiponectin significantly prolonged the lifespan of normal mice. The aim of this study was to elucidate the mechanism involved in the longevity effects of adiponectin using KK/Ta mice, a murine model of metabolic syndrome. We established a Tg line of KK/Ta (Tg-KK/Ta) mice expressing human adiponectin in the liver, and assessed their lifespan. The cause of death was determined by macroscopic and microscopic examinations immediately after death. The expressions of SIRT1, C-reactive protein (CRP), inflammatory cytokines, AMPK, and AKT were measured by quantitative real-time PCR, ELISAs, and/or western blotting. KK/Ta mice had lower serum adiponectin levels and shorter lifespan (57 . 6G13 . 9 vs 106 . 5G18 . 3 weeks, P!0 . 0001) than C57BL/6N mice. Tg adiponectin expression significantly extended the lifespan of KK/Ta mice (73 . 6G16 . 6 weeks, P!0 . 001) without affecting body weight, daily food consumption, or plasma glucose levels. Neoplasms were observed in only three of 22 KK/Ta mice that died spontaneously because of tumors. Atherosclerotic lesions were not detected in any mice. SIRT1 levels were not significantly different between KK/Ta and Tg-KK/Ta mice. Gene expressions of Crp, Tnfa, Il6, and Nfkb were increased in KK/Ta mice, but they were significantly attenuated in Tg-KK/Ta mice. Phosphorylated AMPK levels were increased and phosphorylated AKT levels were decreased in Tg-KK/Ta mice. The anti-inflammatory effects of adiponectin, achieved by inhibiting the AKT signaling pathway, may explain how adiponectin slows the accelerated aging process associated with the metabolic syndrome.

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Mindin: a novel marker for podocyte injury in diabetic nephropathy

Abstract: Mindin could be related to podocyte injury and appears to be an early biomarker of the progression of diabetic nephropathy.

Cited by 33 publications

References 29 publications

The Prevalence and Management of Diabetic Nephropathy in Asia

The Prevalence and Management of Diabetic Nephropathy in Asia

Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic nephropathy

Hyperadiponectinemia protects against premature death in metabolic syndrome model mice by inhibiting AKT signaling and chronic inflammation

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