Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer

Rajan, Teena; Umapathy, Dhamodharan; Jayasuriya, Ravichandran; Ali, Daoud; Kesavan, Rajesh; Ramkumar, Kunka Mohanram

doi:10.1016/j.arcmed.2020.10.011

Cited by 10 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BNIP3 , as a transcription target responding to dysfunctional mitochondria, regulates mitochondrial autophagy mainly by interacting with LC-3 and its related molecular receptors ( 37 ). In hypoxia, HIF-1α can be upregulated to promote BNIP3 expression and limit reactive oxygen species (ROS) production through mitochondrial phagocytosis ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification

Miao¹,

Li²,

Chen³

et al. 2023

Ann Transl Med

View full text Add to dashboard Cite

Background Molecular changes are closely related to the pathogenesis and healing process of diabetic foot ulcers (DFUs), and are crucial for the early prediction and intervention of DFU. Methods Bioinformatics analysis was performed in this study to identify the key differentially expressed genes (DEGs) in DFU, analyze their functions and function modes, and conduct preliminary experimental verification to determine the potential pivotal genes in the pathogenesis of DFU. Two datasets, GSE68183 and GSE80178, were obtained from the Gene Expression Omnibus (GEO). DEGs were obtained using GEO2R. Six co-expressed DEGs (co-DEGs) were obtained by R language analysis. The co-DEGs were constructed by using STRING and Cytoscape 3.7.2 to construct a protein-protein interaction (PPI) network, and two hub genes, NHLRC3 and BNIP3 , were identified. The BNIP3 gene was selected for further analysis. Co-DEGs were used for Gene Ontology (GO) function analysis using the WebGestalt database, and BNIP3 -related biological processes focused on mitochondrial protein decomposition. GO function analysis of the BNIP3 gene and its interacting genes was carried out using the cluster profile package and org.hs.eg. db package of the R language and its biological process was enriched in the cell response to external stimuli and autophagy. Results BNIP3 and its interacting genes were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and KEGG pathway enrichment analysis was performed using the WebGestalt database. The results showed that BNIP3 was significantly correlated with mitochondrial autophagy and the FoxO signaling pathway. The miRDB and TargetScan databases were used to identify the relevant microRNAs (miRNAs) regulating the BNIP3 gene, and it was found that miRNA-182 may be involved in the targeted regulation of BNIP3. Western blot analysis was performed to determine the abnormal expression of BNIP3 . Conclusions Our study found that the BNIP3 gene may be a new biomarker and intervention target for DFU.

show abstract

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification

Miao¹,

Li²,

Chen³

et al. 2023

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…NRF2 plays a crucial role in wound healing by regulating new blood vessel formation. The effect of the NRF2 SNP rs35652124 on function and its association with type 2 diabetes and diabetic foot ulcers have been studied previously (10) .…”

Section: Discussionmentioning

confidence: 99%

Study of Nuclear Factor Erythroid Related Factor 2 Gene Polymorphism in Patients with Type 2 Diabetes Mellitus

Aly¹,

Younes²,

Ahmed³

et al. 2023

The Egyptian Journal of Hospital Medicine

View full text Add to dashboard Cite

Background: The molecular mechanisms that downregulate the nuclear factor erythroid related factor 2 (NRF2) expression in addition to gene polymorphism among type 2 diabetes mellitus (T2DM) patients. Objective: To investigating possible association between NRF2 gene polymorphism with T2DM development. Patients and Methods: This case-control study included 81 persons who were categorized into three groups; The first group, made up of 27 healthy people, served as a control, group 2 consisted of twenty-seven type 2 diabetics without foot ulcers, and group 3 consisted of twenty-seven patients with diabetic foot ulcer who had type 2 diabetes. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to do genotyping of NRF2 (rs35652124) single nucleotide gene polymorphism. Results: Concerning NRF2 genotyping in the investigated groups, 18 (67%) of controls possessed the CC genotype, while 7 (26%) possessed the CT genotype, and 2 (7%) possessed the TT genotype. Eight (30%) of cases in the cases group had the CC genotype, while 13% had CT genotype and 48% had TT genotype. Cases had a far higher frequency of the CT and TT genotypes than controls did. In terms of NRF2 allele distribution, we found that although 43 (80%) of controls and 11 (20%) of controls carried the C allele, 29 (54%) of patients carried the C allele and 25 (46%) of cases carried the T allele. T2DM patients had a significantly greater frequency of T alleles than control subjects. Conclusion: Regarding NRF2 genotyping, our study revealed that TT genotypes and T alleles were statistically significantly higher among patients' group (diabetic with and without diabetic foot) compared to controls. NRF2 gene has a proper value in prediction of T2DM.

show abstract

“…However, compared to nondiabetic wounds, higher levels of oxidative stress were present in the tissue of DFU [47]. The increased sorbitol pathway activity is one of the important mechanisms for the development of DFU [88].…”

Section: Polyol Pathwaysmentioning

confidence: 97%

“…Under hyperglycemia, the activation of Nrf2 is inhibited, and the expression of antioxidant genes including NQO1 and HO1 are significantly down-regulated, which exacerbates the occurrence and development of oxidative stress [37]. The study of Rajan Teena et al [47] using human clinical specimens showed that Nrf2 expression was significantly reduced in type 2 DM subjects and DFU subjects compared with normal glucose tolerant subjects. Perilesional skin tissues from patients with diabetes are often in a more severe state of oxidative stress.…”

Section: Nrf2 Signaling Pathwaysmentioning

confidence: 99%

Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

Song¹,

Liu²,

Liu³

et al. 2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Difficult or even non-healing diabetic foot ulcers (DFU) are a global medical challenge. Although current treatments such as debridement, offloading, and infection control have resulted in partial improvement in DFU, the incidence, amputation, and mortality rates of DFU remain high. Therefore, there is an urgent need to find new or more effective drugs. Numerous studies have shown that oxidative stress plays an important role in the pathophysiology of DFU. The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway and the advanced glycated end products (AGEs)-receptor for advanced glycation endproducts (RAGE), protein kinase C (PKC), polyol and hexosamine biochemical pathways play critical roles in the regulation of oxidative stress in the body. Targeting these pathways to restore redox balance can control and alleviate the occurrence and development of DFU. Natural biologics are a major source of potential drugs for these relevant targets, and their antioxidant potential has been extensively demonstrated. Here, we discussed the pathophysiological mechanism of oxidative stress in DFU, and identifiled natural biologics targeting these pathways to accelerate DFU healing, in order to provide a new or potential direction for clinical treatment, nursing and related basic research of DFU.

show abstract

Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer

Cited by 10 publications

References 30 publications

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification

Study of Nuclear Factor Erythroid Related Factor 2 Gene Polymorphism in Patients with Type 2 Diabetes Mellitus

Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

Contact Info

Product

Resources

About