Involvement of glomerular SREBP-1c in diabetic nephropathy

Ishigaki, Naomi; Yamamoto, Takashi; Shimizu, Yoshio; Kobayashi, Kazuto; Yatoh, Shigeru; Sone, Hirohito; Takahashi, Akimitsu; Suzuki, Hiroaki; Yamagata, Kunihiro; Yamada, Nobuhiro; Shimano, Hitoshi

doi:10.1016/j.bbrc.2007.10.038

Cited by 58 publications

(58 citation statements)

References 27 publications

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“…Several factors, including sterol regulatory element binding protein (SREBP)-1 and Toll-like receptor (TLR) 4, have been shown to mediate lipid nephrotoxicity [32,33]. The expression of SREBP-1, an important regulator of cellular lipid synthesis [34], is upregulated in STZ-induced diabetic rats.…”

Section: Impairment Of the Renal Function By Lipidsmentioning

confidence: 99%

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Dyslipidemia in diabetic nephropathy

2016

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Diabetic nephropathy (DN) not only is a major cause of end-stage renal disease (ESRD) in developing and developed countries but also plays a critical role as a risk factor for cardiovascular disease. The pathogenesis of DN is multifactorial and remains to be elucidated. It is well known that dyslipidemia is frequently complicated with diabetes. Recently, dyslipidemia has been recognized to be involved in the progression of DN. In general, diabetic dyslipidemia is caused by impaired action of lipoprotein lipase (LPL) that is localized to the endothelial cells, resulting in increased serum levels of increased triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C). Smaller size and modified low-density lipoprotein (LDL), such as glycated and oxidized LDL, play important roles to induce vascular and renal cellular dysfunction. Previous studies demonstrated that dyslipidemia enhances macrophage infiltration and excessive extracellular matrix (ECM) production in the glomeruli under diabetic conditions, leading to the development of DN. Clinical studies have demonstrated that lipid-lowering therapy shows a protective effect on the renal function. It is well known that statins reduce albuminuria in patients with DN. A series of our studies indicated that this effect is mediated by Rho-kinase inhibition. Rho-kinase plays a key role in the pathogenesis of DN by activating the inflammatory pathway, including oxidative stress, NF-κB, and hypoxia inducible factor (HIF)-1. Intriguingly, Rho-kinase inhibitors have been shown to attenuate glomerulosclerosis as well as atherosclerosis. Therefore, Rho-kinase could be a promising therapeutic target for both DN and cardiovascular disease.

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Section: Impairment Of the Renal Function By Lipidsmentioning

confidence: 99%

“…Interestingly, the progression of DN is inhibited in SREBP-1-deficient mice. The development of DN is also inhibited in TLR4-deficient mice fed a high-fat diet [32,33].…”

Section: Impairment Of the Renal Function By Lipidsmentioning

confidence: 99%

Dyslipidemia in diabetic nephropathy

2016

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“…Increase in TG, T-CH, VLDL-CH, and LDL-CH in STZ diabetic rats is the result of increased breakdown of lipids, mobilization of free fatty acids from the peripheral stores or increased renal TG synthesis (Ishigaki et al, 2007;Sun et al, 2002). Administration of PGFF for 28 d not only lowered the T-CH, TG, LDL-CH, and VLDL-CH but also enhanced the HDL-CH which is considered to be a protective lipid.…”

Section: Body Weight (G)mentioning

confidence: 99%

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Ankita

Deepti

Nilam

2014

Pharmaceutical Biology

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Context: Different parts of Punica granatum Linn. (Punicaceae) are traditionally used as renal protective agents in the Indian system of medicine. However, there is paucity of information regarding its role in diabetic nephropathy. Objective: The present study investigates the nephroprotective potential of flavonoid-rich fraction of P. granatum leaves in streptozotocin (STZ)-induced early diabetic nephropathy in experimental animals. Materials and methods: Experimental diabetic nephropathy was induced in Wistar rats by single intraperitonial injection of STZ (65 mg/kg) dissolved in ice cold citrophosphate buffer (pH 4.3). After induction rats were divided into five groups (6 normal; 24 diabetic) and administered with glibenclamide (5 mg/kg) and three dose levels of flavonoid-rich fraction of P. granatum leaves (PGFF), i.e. 50, 100, and 200 mg/kg body weight/day for 28 d. Fasting blood glucose, lipid profile, serum albumin, serum total protein, serum creatinine, blood urea nitrogen (BUN) glycosylated hemoglobin, and biomarkers of kidney oxidative stress were assessed at the end of the treatment period. Urine was analyzed for the measurement of total protein, albumin, and creatinine clearance. Kidney sections were subjected to histopathological study. Results: Daily oral administration of variable dose levels of PGFF for 28 d normalized various biochemical, metabolic, and histopathological changes in the diabetic rats. PGFF significantly (p50.01 and p50.05) improved the glycemic status and renal function in diabetic rats as compared with diabetic control rats. Discussion and conclusion: The results of our study thus prove the protective effect of PGFF in early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals.

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“…Furthermore, in the diabetic rat, the stimulation of expression of NADPH oxidase was noted to be increased in the kidney and NADPH oxidase dependent overproduction of ROS plays a key role in the induction of renal hypertrophy and nephropathy [23,27] . Intriguingly, activation of glomerular SREBP-1 increases NADPH oxidase-mediated ROS production, which further progresses diabetic nephropathy [28] . Thus, this evidence suggests a possible pathological role of NADPH in diabetic nephropathy.…”

Section: Of Nephropathymentioning

confidence: 99%

Smoking in diabetic nephropathy: sparks in the fuel tank?

Chakkarwar¹

2012

WJD

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Diabetic nephropathy is associated with high morbidity and mortality and the prevalence of this disease is continuously increasing worldwide. Long-term diabetes increases the likelihood of developing secondary complications like nephropathy, the most common cause of end stage renal disease. Usually, other factors like hypertension, alcoholism and smoking also partly contribute to the progression of diabetic nephropathy. Among this, cigarette smoking in diabetes has been repeatedly confirmed as an independent risk factor for the onset and progression of diabetic nephropathy. Various studies suggest that smoking is a major fuel in the development of high oxidative stress and subsequently hyperlipidemia, accumulation of advanced glycation end products, activation of the renin angiotensin system and Rho-kinase, which are observed to play a pathogenic role in the progression of diabetic nephropathy. Furthermore, cigarette smoking in diabetic patients with vascular complications produces a variety of pathological changes in the kidney, such as thickening of the glomerular basement membrane and mesangial expansion with progression in glomerulosclerosis and interstitial fibrosis, which ultimately results in end stage renal failure. Strong associations are consistently found between chronic cigarette smoking and diabetic microvascular complications. A diverse group of studies unveil potential mechanisms that may explain the role of cigarette smoking in the progression of diabetic nephropathy. Tremendous efforts are being made to control smoking mediated progression of diabetic nephropathy, but no promising therapy is yet available. The present review critically discusses the possible detrimental role of chronic cigarette smoking in the progression of diabetic nephropathy and various possible pharmacological interventions to attenuate the exacerbation of diabetic nephropathy.

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Involvement of glomerular SREBP-1c in diabetic nephropathy

Cited by 58 publications

References 27 publications

Dyslipidemia in diabetic nephropathy

Dyslipidemia in diabetic nephropathy

Flavonoid rich fraction ofPunica granatumimproves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Smoking in diabetic nephropathy: sparks in the fuel tank?

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