Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

Nie, Ping; Yan, Lianshan; Bai, Xue; Zhu, Yongtong; Guo, Qi; Luo, Ping; Zhang, Weiguang; Li, Bing

doi:10.1038/s41387-022-00212-4

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…Just one study investigated the expression levels of Nrf2 in patients with DKD. 11 In this study, in series of 30 patients with DKD, Nrf2 levels were reduced as compared with healthy individuals and were associated with reduced levels of serum zinc. In the present study, Nrf2 levels were selectively reduced in patients with DKD but similar in patients with diabetes without DKD and in controls, suggesting that this factor impacts on kidney damage in DKD.…”

Section: Discussionmentioning

confidence: 61%

“…Notwithstanding its fundamental role in oxidative stress processes and its potential relevance in kidney damage in experimental models,6 Nrf2 gene expression levels have been largely overlooked in clinical research in patients with type 2 diabetes. Just one study investigated the expression levels of Nrf2 in patients with DKD 11. In this study, in series of 30 patients with DKD, Nrf2 levels were reduced as compared with healthy individuals and were associated with reduced levels of serum zinc.…”

Section: Discussionmentioning

confidence: 96%

“…The role of Nrf2 in the pathogenesis of DKD has been sparsely investigated in patients with type 2 diabetes10 and, to our knowledge, the expression levels of Nrf2 have been examined in just one study in patients with DKD 11. No observation has been until now produced on Nrf2 and its regulators, namely miRNAs that can potentially inhibit the Nrf2 signaling pathway and Keap1, in DKD.…”

Section: Introductionmentioning

confidence: 99%

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Role of kidney function on Nrf2 mRNA levels in type 2 diabetes

Spoto,

Politi,

Postorino

et al. 2024

BMJ Open Diab Res Care

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IntroductionDiabetic kidney disease (DKD) is a major complication in patients with diabetes and the main contributor to the chronic kidney disease (CKD) global burden. Oxidative stress is a crucial factor in DKD pathogenesis but the role of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and its molecular regulators has been poorly investigated in man.Research design and methodsIn this case-control study, we analyzed the roles of Nrf2, a transcription factor shielding cells from oxidative stress, its repressor Kelch-like ECH-associated protein 1 (Keap1) and six microRNAs (miRNAs) that potentially suppress Nrf2. We categorized 99 participants into 3 groups: 33 non-dialysis patients with type 2 diabetes with DKD, 33 patients with type 2 diabetes without DKD and 33 control subjects and quantified the gene expression (messenger RNA (mRNA)) levels of Nrf2, Keap1 and 6 miRNAs. Moreover, we studied the correlation between gene expression levels and clinical indicators of kidney health.ResultsIn patients with diabetes with DKD, Nrf2 mRNA levels were significantly lower than in patients without DKD (p=0.01) and controls (p=0.02), whereas no difference in Nrf2 expression levels existed between patients without DKD and controls. Conversely, in patients with and without DKD, Keap1 expression levels were significantly higher than in controls. Of the six miRNAs studied, miRNA 30e-5p showed differential expression, being markedly reduced in patients with DKD (p=0.007). Nrf2 mRNA levels directly correlated with estimated glomerular filtration rate (eGFR) in patients with DKD (r=0.34, p=0.05) and in a formal mediation analysis the eGFR emerged as the first factor in rank for explaining the difference in Nrf2 mRNA levels between patients with and without DKD.ConclusionsThe observed dysregulation in the Nrf2-Keap1 axis and the unique expression pattern of miRNA30e-5p in DKD underscore the need for more focused research in this domain that can help identify novel intervention strategies for DKD in patients with type 2 diabetes.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Role of kidney function on Nrf2 mRNA levels in type 2 diabetes

Spoto,

Politi,

Postorino

et al. 2024

BMJ Open Diab Res Care

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“…In addition, the degree of mesangial expansion, the incidence of K-W nodules and capillary micro-aneurysms were also found to be more severe and signi cant in the kidneys of patients in the low-Zn group than in the normal-Zn group [21]. Our study revealed that plasma Zn levels were lower in patients with DN than those in healthy controls, consistent with the ndings of Feng et al [10,21,22]. Moreover, patients with lower Zn levels had higher in ammatory factors in the renal tissue and signi cantly more urinary protein excretion, indicating more severe renal injury.…”

Section: Discussionmentioning

confidence: 92%

Influence of zinc levels on clinical and inflammatory factors, and renal prognosis in patients with diabetic nephropathy

Li,

Zhu,

Luo

et al. 2023

Preprint

Self Cite

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Background/Objectives: Our study aimed to investigate the correlation of plasma zinc (Zn)with tumor necrosis factor-α (TNF-α), non-classical nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) in patients with diabetic nephropathy (DN༉and explored the potential impact of Zn levels on clinical, inflammatory responses and renal prognosis in DN patients. Subjects/Methods: We selected 45 patients who were definitively diagnosed with DN by renal biopsy in our hospital from 2019 to 2021, and recruited 25 healthy individuals from the physical examination center as controls. The correlation between Zn and serum Nrf2, TNF-α, and NF-κB levels were assessed using Spearman's rank correlation coefficient. In addition, patients were further divided into low- and high-Zn groups to observe the differences in clinical indicators, identify the expression of inflammatory-related factors in renal tissue. The Kaplan–Meier method was used to draw survival curves to predict the impact of related indicators on renal prognosis. Results We found that blood Zn and Nrf2 levels in patients with DN were significantly lower, while TNF-α, and NF-κB levels were significantly higher than those in patients without DN. Zn correlated positively with Nrf2 levels and negatively with TNF-α and NF-κB levels. In addition, patients with high Zn levels had higher expression of Nrf2, and lower expression levels of TNF-α and NF-κB in renal tissue, and had better prognosis compared with patients with low Zn levels. Conclusions We demonstrated that Zn had a protective effect on DN, and it may affect the inflammatory response.

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“…Diabetic patients, in particular, require an adequate level of zinc to ensure Nrf2 activation, which protects them against diabetes-induced oxidative damage to their bones and several other organs [141,142].…”

Section: Melatoninmentioning

confidence: 99%

Bone Formation and Maintenance in Oral Surgery: The Decisive Role of the Immune System—A Narrative Review of Mechanisms and Solutions

Choukroun,

Parnot,

Surmenian

et al. 2024

Bioengineering

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Based on the evidence of a significant communication and connection pathway between the bone and immune systems, a new science has emerged: osteoimmunology. Indeed, the immune system has a considerable impact on bone health and diseases, as well as on bone formation during grafts and its stability over time. Chronic inflammation induces the excessive production of oxidants. An imbalance between the levels of oxidants and antioxidants is called oxidative stress. This physio-pathological state causes both molecular and cellular damage, which leads to DNA alterations, genetic mutations and cell apoptosis, and thus, impaired immunity followed by delayed or compromised wound healing. Oxidative stress levels experienced by the body affect bone regeneration and maintenance around teeth and dental implants. As the immune system and bone remodeling are interconnected, bone loss is a consequence of immune dysregulation. Therefore, oral tissue deficiencies such as periodontitis and peri-implantitis should be regarded as immune diseases. Bone management strategies should include both biological and surgical solutions. These protocols tend to improve immunity through antioxidant production to enhance bone formation and prevent bone loss. This narrative review aims to highlight the relationship between inflammation, oxidation, immunity and bone health in the oral cavity. It intends to help clinicians to detect high-risk situations in oral surgery and to propose biological and clinical solutions that will enhance patients’ immune responses and surgical treatment outcomes.

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Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

Cited by 10 publications

References 36 publications

Role of kidney function on Nrf2 mRNA levels in type 2 diabetes

Role of kidney function on Nrf2 mRNA levels in type 2 diabetes

Influence of zinc levels on clinical and inflammatory factors, and renal prognosis in patients with diabetic nephropathy

Bone Formation and Maintenance in Oral Surgery: The Decisive Role of the Immune System—A Narrative Review of Mechanisms and Solutions

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