Glucose Induces Clonal Selection and Reversible Dinucleotide Repeat Expansion in Mesangial Cells Isolated from Glomerulosclerosis-Prone Mice

Fornoni, Alessia; Lenz, Oliver; Striker, Liliane J.; Striker, Gary E.

doi:10.2337/diabetes.52.10.2594

Cited by 12 publications

(10 citation statements)

References 38 publications

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“…43 Although not applicable to aging, per se, stable epigenetic changes in the matrix metalloproteinase-9 promoter could be induced by chronic hyperglycemia in vitro, a condition associated with increased formation of AGEs and increased OS. 48,49 We found that the reversibility of the phenotypic changes in the matrix metalloproteinase-9 promoter depended on the genetic background. 49 …”

Section: Studies In Micementioning

confidence: 87%

“…Namely, the stable phenotypic changes in mesangial cells in vitro reflect the in vivo sclerotic glomerular changes. 47,48 The stable aging phenotype is proinflammatory and prosclerotic, as shown by gene expression analysis that revealed that the stable phenotypic changes in glomerular cells were proinflammatory and prosclerotic. 43 Although not applicable to aging, per se, stable epigenetic changes in the matrix metalloproteinase-9 promoter could be induced by chronic hyperglycemia in vitro, a condition associated with increased formation of AGEs and increased OS.…”

Section: Studies In Micementioning

confidence: 99%

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Identifying Advanced Glycation End Products as a Major Source of Oxidants in Aging: Implications for the Management and/or Prevention of Reduced Renal Function in Elderly Persons

Vlassara

Uribarri

Ferrucci

et al. 2009

Seminars in Nephrology

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Summary Aging is characterized by increasing inflammation and oxidant stress (OS). Reduced renal function was present in more than 20% of normal-aged individuals sampled in the National Health and Nutrition Examination Survey (NHANES) cross-sectional study of the US population. Longitudinal studies in the United States and Italy showed that renal function does not decline in some individuals, suggesting that a search for causes of the loss of renal function in some persons might be indicated and interventions to reduce this outcome should be sought. Because advanced glycation end products (AGEs) induce both inflammation and OS, accumulate with age, and primarily are excreted by the kidney, one outcome of reduced renal function in aging could be decreased AGE disposal. The build-up of AGEs with reduced renal function could contribute to inflammation, increased oxidant stress, and accumulation of AGEs in aging. In fact, results from a longitudinal study of normal aging adults in Italy showed that the most significant correlation with mortality was the level of renal function. A clear link between inflammation, OS, AGEs, and chronic disease was shown in studies of mice that showed that reduction of AGE levels by drugs or decreased intake of AGEs reduces chronic kidney disease (CKD) and cardiovascular disease of aging. The data support a role for AGEs in the development of renal lesions in aging mice and reveal that AGEs in the diet are very important contributors to renal and cardiovascular lesions. AGEs signal through two receptors, one of which is anti-inflammatory (AGER1) and the other is proinflammatory (RAGE). Overexpression of AGER1 protects against OS and acute vascular injury. The reduction of AGEs in the diet is as efficient in preventing aging-related cardiovascular and renal lesions in mice as that seen with calorie restriction. Studies in normal adults of all ages and those with CKD suggest that the findings in mice may be directly applicable to both aging and CKD. Namely, the dietary content of AGEs determines the serum levels of AGEs and inflammatory mediators and urine AGE levels in both normal subjects and CKD patients. Importantly, reduction of AGEs controls these changes in both normal subjects and CKD patients, and the phenotypic changes in AGER1 are reduced in CKD patients by decreasing the amount of AGEs consumed with the diet. These data suggest that the changes in renal function in normal aging may be subject to control and this subject deserves renewed attention.

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Section: Studies In Micementioning

confidence: 87%

Section: Studies In Micementioning

confidence: 99%

Identifying Advanced Glycation End Products as a Major Source of Oxidants in Aging: Implications for the Management and/or Prevention of Reduced Renal Function in Elderly Persons

Vlassara

Uribarri

Ferrucci

et al. 2009

Seminars in Nephrology

Self Cite

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“…For example, in a recent study, Fornoni et al observed that exposure of mesangial cells to high glucose concentrations in vitro induced MSI. Thus, dietary sugars, such as refined glucose, may create conditions to produce significant structural and biological alterations that might include genomic instability within DNA (31).…”

Section: Discussionmentioning

confidence: 99%

Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study

Satia

Keku

Galanko

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: Microsatellite instability (MSI) is one form of genomic instability that occurs in 10% to 20% of sporadic colon tumors and almost all hereditary nonpolyposis colon cancers. However, little is known about how environmental factors (e.g., diet) may influence MSI in sporadic colon cancer. Methods: We used data from a population-based casecontrol study in North Carolina (486 colon cancer cases and 1,048 controls) to examine associations of diet (total energy, macronutrients, micronutrients, and food groups) with MSI. In-person interviews elicited information on potential colon cancer risk factors, and a previously validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year before diagnosis or interview date. MSI was classified as MSI-high (MSI-H) and MSI-low or microsatellite stable (MSI-L/MSS). Multivariate logistic regression models estimated energy-adjusted and non-energy-adjusted odds ratios (OR).Results: Ten percent of the cases (n = 49) had MSI-H tumors (29% African American). The strongest associations between diet and MSI were observed in case-control comparisons: there was a robust inverse association between MSI-H status and B-carotene [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.9] and positive associations with energy-adjusted refined carbohydrates (OR, 2.2; 95% CI, 0.9-5.4) and non-energy-adjusted read meat intake (OR, 2.0; 95% CI, 0.9-4.2). Compared with controls, MSI-L/MSS tumors were statistically significantly associated with energy-adjusted vitamin C, vitamin E, calcium, dietary fiber, and dark green vegetables and positively associated with total energy intake (all Ps for trend < 0.05). In case-case comparisons, no dietary factors were significantly differently related to MSI-H compared with MSI-L/MSS tumors. Conclusion: Refined carbohydrate and red meat consumption may promote development of MSI-H tumors, whereas B-carotene may be associated with lower risk.

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“…Studies of Os/ϩ ROP mice show that they possess approximately 50% fewer nephrons in the Os/ϩ mice than in the ϩ/ϩ mice (160). In general, wild-type mice (Os ϩ/ϩ , Ra ϩ/ϩ , and Pt ϩ/ϩ ) of ROP background seem to be more prone to glomerulosclerosis than C57BL/6 mice after a reduction in renal mass (161)(162)(163). Mice on the ROP background, in the absence of Os, Ra, or Pt mutant alleles, may also exhibit increased propensity for glomerulosclerosis after combined nephron mass reduction and diabetes (146).…”

Section: Ropmentioning

confidence: 99%

Mouse Models of Diabetic Nephropathy

Breyer¹,

Böttinger²,

Brosius³

et al. 2005

Journal of the American Society of Nephrology

483

516

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Mice provide an experimental model of unparalleled flexibility for studying mammalian diseases. Inbred strains of mice exhibit substantial differences in their susceptibility to the renal complications of diabetes. Much remains to be established regarding the course of diabetic nephropathy (DN) in mice as well as defining those strains and/or mutants that are most susceptible to renal injury from diabetes. Through the use of the unique genetic reagents available in mice (including knockouts and transgenics), the validation of a mouse model reproducing human DN should significantly facilitate the understanding of the underlying genetic mechanisms that contribute to the development of DN. Establishment of an authentic mouse model of DN will undoubtedly facilitate testing of translational diagnostic and therapeutic interventions in mice before testing in humans.J (1), with costs for care of these patients projected to be $12 billion/yr by 2010 (1). Despite the high prevalence of DN, only 20 to 40% of all diabetic patients are prone to developing kidney failure, and family-based studies suggest that a significant genetic component confers risk for DN (2-4). Studies of diabetic mice suggest that, like people, mice exhibit differential susceptibility to diabetes and renal and cardiovascular diseases (5-7). In mice, identification of a strain that is prone to disease provides the relevant discriminator rather than identification of an individual who is at risk for diabetic complications. However, in contrast to people, each inbred mouse strain represents a genetically homogeneous and readily replenished resource that is amenable to repeated experimental study.Biomedical experimentation in mice affords significant advantages over experimentation in other species. These advantages include the development of diverse and unique genetic resources, including completion of a detailed map of murine genomic sequence that is freely available through the internet, as well as Ͼ450 inbred strains of mice that have been generated over the past century, with each strain genetically being homogeneous and offering a unique array of phenotypes (8,9). The availability of murine embryonic stem cells has also provided the ability to disrupt the expression and function of specific preselected genes (10 -12). Finally, repositories of mice that bear multiple mutations that alter function in each known gene are gradually being assembled (13-15). These unique resources have the potential to significantly facilitate studies into the pathogenesis of disease in mice. Through the use of the unique genetic reagents that are available in mice (including knockouts and transgenics), the identification of a robust mouse model of DN should significantly facilitate understanding of the underlying genetic mechanisms that contribute to the development of DN in people as well as in mice. Establishment of a valid mouse model of DN should also facilitate testing of translational diagnostic and therapeutic interventions in mice before testing in humans. Workin...

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Glucose Induces Clonal Selection and Reversible Dinucleotide Repeat Expansion in Mesangial Cells Isolated from Glomerulosclerosis-Prone Mice

Cited by 12 publications

References 38 publications

Identifying Advanced Glycation End Products as a Major Source of Oxidants in Aging: Implications for the Management and/or Prevention of Reduced Renal Function in Elderly Persons

Identifying Advanced Glycation End Products as a Major Source of Oxidants in Aging: Implications for the Management and/or Prevention of Reduced Renal Function in Elderly Persons

Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study

Mouse Models of Diabetic Nephropathy

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