Improvements in the Management of Diabetic Nephropathy

Dounousi, Evangelia; Duni, Αnila; Leivaditis, Konstantinos; Vaios, Vasilios; Eleftheriadis, Theodoros; Liakopoulos, Vassilios

doi:10.1900/rds.2015.12.119

Cited by 70 publications

(56 citation statements)

References 154 publications

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“…In theory, Fibulin-3 may be effective in reducing vascular calcification in other pathologies associated with oxidative stress such as diabetes mellitus [73, 74] or aging [28, 75]. Fibulin-3 expression is decreased with aging [52] and Fibulin-3 deficiency in mice leads to early onset of aging-associated phenotypes [76].…”

Section: Discussionmentioning

confidence: 99%

Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress

Luong

Schelski

Boehme

et al. 2018

Cell Physiol Biochem

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Background/Aims: Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification. Methods: Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress. Results: Treatment with calcification medium significantly increased calcium deposition in HAoSMCs, an effect significantly blunted by additional treatment with Fibulin-3. Moreover, phosphate-induced alkaline phosphatase activity and mRNA expression of osteogenic and chondrogenic markers MSX2, CBFA1, SOX9 and ALPL were all significantly reduced by addition of Fibulin-3. These effects were paralleled by similar regulation of oxidative stress in HAoSMCs. Phosphate treatment significantly up-regulated mRNA expression of the oxidative stress markers NOX4 and CYBA, down-regulated total antioxidant capacity and increased the expression of downstream effectors of oxidative stress PAI-1, MMP2 and MMP9 as well as BAX/BLC2 ratio in HAoSMCs, all effects blocked by additional treatment with Fibulin-3. Furthermore, the protective effects of Fibulin-3 on phosphate-induced osteogenic and chondrogenic markers expression in HAoSMCs were reversed by additional treatment with hydrogen peroxide. Conclusions: Fibulin-3 attenuates phosphate-induced osteo-/ chondrogenic transdifferentiation and calcification of VSMCs, effects involving inhibition of oxidative stress. Up-regulation or supplementation of Fibulin-3 may be beneficial in reducing the progression of vascular calcification during hyperphosphatemic conditions such as CKD.

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Section: Discussionmentioning

confidence: 99%

Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress

Luong

Schelski

Boehme

et al. 2018

Cell Physiol Biochem

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“…The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS) [64]. As discussed earlier in this review, epigenetic regulation of DNA and histones plays important parts in DN.…”

Section: Epigenetic and Ncrna-based Therapymentioning

confidence: 99%

Epigenetic Regulations in Diabetic Nephropathy

Liu

Feng

2017

Journal of Diabetes Research

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Diabetic nephropathy (DN) is a chronic complication of diabetes and the most common cause of end-stage kidney disease. It has been reported that multiple factors are involved in the pathogenesis of DN, while the molecular mechanisms that lead to DN are still not fully understood. Numerous risk factors for the development of diabetic nephropathy have been proposed, including ethnicity and inherited genetic differences. Recently, with the development of high-throughput technologies, there is emerging evidence that suggests the important role of epigenetic mechanisms in the pathogenesis of DN. Epigenetic regulations, including DNA methylation, noncoding RNAs, and histone modifications, play a pivotal role in DN pathogenesis by a second layer of gene regulation. All these findings can contribute to developing novel therapies for DN.

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“…Carotenoids (such as lutein, zeaxanthin, lycopene, and astaxanthin) as part of the antioxidant system may contribute to attenuate free radical injury, and reduce inflammation, and they may be used as part of an approach to inhibit the complications associated with diabetes [30]. Recent molecules, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial consequences or significant side effects [29]. GLP-1R agonists have impact over glucose control that may have an indirect role in nephroprotection.…”

Section: Discussionmentioning

confidence: 99%

“…Antiproteinuric effects of RAS combination therapy do not seem to augment the prevention of renal disease progression. Combined use of the RAS inhibiting agents was found to be associated with an increased rate of serious adverse events [29].…”

Section: New Pharmacological Strategies and Renal And Cardiovascular mentioning

confidence: 99%