Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy

Fugmann, Tim; Borgia, Beatrice; Révész, Csaba; Godó, Mária; Forsblom, Carol; Hamar, Péter; Holthöfer, Harry; Neri, Dario; Roesli, Christoph

doi:10.1038/ki.2011.116

Cited by 58 publications

(46 citation statements)

References 53 publications

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“…Vanin-1, an epithelial glycosylphos-phatidylinositol-anchored pantetheinase (Aurrand-Lions et al, 1996;Pitari et al, 2000), participates in the response to oxidative stress in vivo (Berruyer et al, 2004). A recent study showed that the protein levels of renal vanin-1 increased in rats with streptozotocin-induced diabetic nephropathy, and urinary vanin-1 was detected in patients with diabetic nephropathy (Fugmann et al, 2011). Therefore, it is anticipated that urinary vanin-1 is a potential biomarker for the early detection of AKI.…”

Section: N-acetyl-␤-d-glucosaminidase (Nag)mentioning

confidence: 99%

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury

Hosohata

Ando²,

Fujimura³

2012

J Pharmacol Exp Ther

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Drug-induced nephrotoxicity is a serious problem in patients with hospital-acquired acute kidney injury (AKI). A new renal biomarker is needed because traditional markers are not sensitive for early detection of drug-induced AKI. In a recent study, we demonstrated that vanin-1 is a novel candidate biomarker of nephrotoxicant-induced kidney injury. The objective of the present study is to determine whether the increase in urinary vanin-1 is detected before the elevations of serum creatinine or urinary N-acetyl-␤-glucosaminidase (NAG), kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL) in the two well established animal models of drug-induced AKI. After the administration of a higher dose of cisplatin (10 mg/kg, a single intraperitoneal dose) or gentamicin (120 mg/kg per day, once daily intraperitoneal dose for 9 days), urinary vanin-1 was detected earlier than the other biomarkers. In rats treated with a lower dose of cisplatin (5 mg/kg, a single intraperitoneal dose) or gentamicin (40 mg/kg per day, once daily intraperitoneal dose for 9 days), serum creatinine and urinary NAG were not changed throughout the study period, whereas urinary vanin-1, Kim-1, and NGAL were significantly increased. The renal vanin-1 protein levels were significantly decreased in rats treated with the higher dose of cisplatin on day 5 and gentamicin on day 9, and the immunofluorescence analyses confirmed that vanin-1 immunoreactivity in tubular cells was reduced with the time after the dose of cisplatin, indicating that urinary vanin-1 was leaked from tubular cells. These results suggest that, compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally sensitive biomarker for drug-induced AKI.

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Section: N-acetyl-␤-d-glucosaminidase (Nag)mentioning

confidence: 99%

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury

Hosohata

Ando²,

Fujimura³

2012

J Pharmacol Exp Ther

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“…Since pantetheinase protein was originally purified from horse kidney and vanin-1/VNN-1 mRNA is abundant in kidney tissue, one can speculate that detection of pantetheinase levels in urea and/or changes in mRNA expression in kidney tissues would reflect renal tissue damage. One report by Fugmann et al (36) showed that concentrations of VNN1 distinguished diabetic patients with macroalbuminuria from those with normal albuminuria. Another report by Hosohata et al (37) showed that urinary pantetheinase is derived from damaged tubular kidney cells.…”

Section: Pantetheinase Family Genes and Proteins As Indicators Of Hummentioning

confidence: 99%

The Linkage Between Coenzyme A Metabolism and Inflammation: Roles of Pantetheinase

Nitto

Onodera

2013

J Pharmacol Sci

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Abstract.Pantetheinase is an enzyme hydrolyzing pantetheine, an intermediate of the coenzyme A degradation pathway. Pantetheinase has long been considered as the enzyme that recycles pantothenic acid (vitamin B 5 ) generated during coenzyme A breakdown. Genetic analyses showed that mammals have multiple genes known as vanin family genes. Recent studies using mice lacking the vanin-1 gene (pantetheinase gene) suggest that pantetheinase is actively involved in the progression of inflammatory reactions by generating cysteamine. Additional studies using human leukocytes demonstrate that human neutrophils have abundant pantetheinase proteins on the surface and inside the cells. The second pantetheinase protein, GPI-80/VNN2, is suggested to work as a modulator of the function of Mac-1 (CD11b/CD18), an adhesion molecule important to neutrophil functions. This review delineates the characteristics of the pantetheinase/vanin gene family and how they affect inflammation.

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“…In the liver, the mRNA expression levels of VNN1, as well as its activity, are induced upon fasting (18,19). A clinical study showed that the concentrations of VNN1 in pooled human urine distinguished diabetic patients with macroalbuminuria from those with normal albuminuria (20). In addition, the combination of VNN1 and MMP9 has been suggested as a novel blood biomarker panel to discriminate pancreatic cancer-associated diabetes from type 2 diabetes (21).…”

mentioning

confidence: 99%

Vanin-1 Is a Key Activator for Hepatic Gluconeogenesis

et al. 2014

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Vanin-1 (VNN1) is a liver-enriched oxidative stress sensor that has been implicated in the regulation of multiple metabolic pathways. Clinical investigations indicated that the levels of VNN1 were increased in the urine and blood of diabetic patients, but the physiological significance of this phenomenon remains unknown.In this study, we demonstrated that the hepatic expression of VNN1 was induced in fasted mice or mice with insulin resistance. Gain-and loss-of-function studies indicated that VNN1 increased the expression of gluconeogenic genes and hepatic glucose output, which led to hyperglycemia. These effects of VNN1 on gluconeogenesis were mediated by the regulation of the Akt signaling pathway. Mechanistically, vnn1 transcription was activated by the synergistic interaction of peroxisome proliferator-activated receptor g coactivator 1a (PGC-1a) and hepatocyte nuclear factor-4a (HNF-4a). A chromatin immunoprecipitation analysis indicated that PGC-1a was present near the HNF-4a binding site on the proximal vnn1 promoter and activated the chromatin structure. Taken together, our results suggest an important role for VNN1 in regulating hepatic gluconeogenesis. Therefore, VNN1 may serve as a potential therapeutic target for the treatment of metabolic diseases caused by overactivated gluconeogenesis.

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Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy

Cited by 58 publications

References 53 publications

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury

The Linkage Between Coenzyme A Metabolism and Inflammation: Roles of Pantetheinase

Vanin-1 Is a Key Activator for Hepatic Gluconeogenesis

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