A protective role of renalase in diabetic nephropathy

Yin, Jianyong; Liu, Xuanchen; Zhao, Ting; Liang, Rulian; Wu, Rui; Zhang, Fangfei; Kong, Yiwei; Liu, Limei; Xing, Tao; Wang, Niansong; Zhao, Qing; Wang, Feng

doi:10.1042/cs20190995

Cited by 18 publications

(29 citation statements)

References 24 publications

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“…These symptoms were ameliorated with renalase overexpression in db/db mice. Renalase exerted the protective effects in DN through inhibition of mesangial cell hypertrophy, oxidative stress, and inflammation [ 35 ]. The results of the molecular studies also showed a linkage between the renalase gene polymorphisms and kidney diseases [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

et al. 2021

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Aims Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). Methods In this case–control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN− (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR− (independently of the presence of DN). Results No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16–1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26–2.75, p = 0.001) than DR− patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). Conclusions This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

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Section: Discussionmentioning

confidence: 99%

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

et al. 2021

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“…In light of the pivotal underlying mechanisms of myocardial fibrosis validated by the fibroblast-specific, in vivo model ( 7 ), the particular focus herein is on the TGF-β and mitogen-activated kinases (MAPKs) pathways, which are evidenced targets by renalase ( 11 , 13 , 16 , 17 , 21 , 68 , 69 ), as presented in Figure 1 .…”

Section: The Identification Of Renalase As a Relevant Antifibrotic Mo...mentioning

confidence: 99%

The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis

Stojanović

Mitić

Stojanović

et al. 2022

Front. Cardiovasc. Med.

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Cardiac fibrosis represents a redundant accumulation of extracellular matrix proteins, resulting from a cascade of pathophysiological events involved in an ineffective healing response, that eventually leads to heart failure. The pathophysiology of cardiac fibrosis involves various cellular effectors (neutrophils, macrophages, cardiomyocytes, fibroblasts), up-regulation of profibrotic mediators (cytokines, chemokines, and growth factors), and processes where epithelial and endothelial cells undergo mesenchymal transition. Activated fibroblasts and myofibroblasts are the central cellular effectors in cardiac fibrosis, serving as the main source of matrix proteins. The most effective anti-fibrotic strategy will have to incorporate the specific targeting of the diverse cells, pathways, and their cross-talk in the pathogenesis of cardiac fibroproliferation. Additionally, renalase, a novel protein secreted by the kidneys, is identified. Evidence demonstrates its cytoprotective properties, establishing it as a survival element in various organ injuries (heart, kidney, liver, intestines), and as a significant anti-fibrotic factor, owing to its, in vitro and in vivo demonstrated pleiotropy to alleviate inflammation, oxidative stress, apoptosis, necrosis, and fibrotic responses. Effective anti-fibrotic therapy may seek to exploit renalase’s compound effects such as: lessening of the inflammatory cell infiltrate (neutrophils and macrophages), and macrophage polarization (M1 to M2), a decrease in the proinflammatory cytokines/chemokines/reactive species/growth factor release (TNF-α, IL-6, MCP-1, MIP-2, ROS, TGF-β1), an increase in anti-apoptotic factors (Bcl2), and prevention of caspase activation, inflammasome silencing, sirtuins (1 and 3) activation, and mitochondrial protection, suppression of epithelial to mesenchymal transition, a decrease in the pro-fibrotic markers expression (’α-SMA, collagen I, and III, TIMP-1, and fibronectin), and interference with MAPKs signaling network, most likely as a coordinator of pro-fibrotic signals. This review provides the scientific rationale for renalase’s scrutiny regarding cardiac fibrosis, and there is great anticipation that these newly identified pathways are set to progress one step further. Although substantial progress has been made, indicating renalase’s therapeutic promise, more profound experimental work is required to resolve the accurate underlying mechanisms of renalase, concerning cardiac fibrosis, before any potential translation to clinical investigation.

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“…Its N-terminal peptide, by binding to the calcium-transporting ATPase PMCA4b, activates the PI3K/AKT and MAPK pathways. In patients with chronic kidney disease, renalase could reduce the expression of mediators involved in the inflammatory response and glomerular fibrosis, such as pro-inflammatory cytokines and NADPH oxidase [ 9 ]. Recombinant renalase diminishes glomerular hypertrophy, interstitial fibrosis, proteinuria, hypertension and myocardial remodeling by decreasing the phosphorylation of ERK-1/2 [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…In patients with chronic kidney disease, renalase could reduce the expression of mediators involved in the inflammatory response and glomerular fibrosis, such as pro-inflammatory cytokines and NADPH oxidase [ 9 ]. Recombinant renalase diminishes glomerular hypertrophy, interstitial fibrosis, proteinuria, hypertension and myocardial remodeling by decreasing the phosphorylation of ERK-1/2 [ 9 ]. It has been shown that renalase may also protect against cisplatin and hydrogen peroxide-induced toxic injury of proximal tubular (HK-2) cells [ 8 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients

Wiśniewska

Serwin

Dziedziejko

et al. 2021

IJERPH

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Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

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A protective role of renalase in diabetic nephropathy

Cited by 18 publications

References 24 publications

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis

The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients

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