Altered expression of WFS1 and NOTCH2 genes associated with diabetic nephropathy in T2DM patients

Sharaf, Sahar A.; Kantoush, Nagwa; Ayoub, Dina F.; Ibrahim, Alshaymaa A.; Abdelaal, Amaal A.; Aziz, Rokaya Abdel; ElHefnawi, Mahmoud; Ahmed, A. A. I.

doi:10.1016/j.diabres.2018.03.053

Cited by 13 publications

(10 citation statements)

References 38 publications

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“…The occurrence and development of DN may be caused by oxidative stress, inflammatory reactions, glucose and lipid metabolism disorders, and other factors [10, 11]. These factors activate multiple signaling pathways in the kidney [12–14], which may contribute to the pathogenesis of DN.…”

Section: Introductionmentioning

confidence: 99%

The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways

Zhao

Yang

et al. 2019

BioMed Research International

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The study aims to investigate the effects of the alcohol extract of Coreopsis tinctoria Nutt (AC) on diabetic nephropathy (DN) mice. A total of 30 db/db (DN) mice were divided into 3 groups, which were treated with AC (300 mg/kg/day), metformin (180 mg/kg/day), or saline by gavage for 10 weeks. Ten db/m mice treated with saline were used as normal control (NC group). Body weight (BW) and fasting blood glucose (FBG), HbA1c, 24 h urinary albumin excretion (UAE), and renal pathological fibrosis were analyzed. Expression of miR-192, miR-200b, and proteins in the PTEN/PI3K/AKT pathway was analyzed by qPCR or western blot. The DN mice had significantly higher BW, FBG, and 24 h UAE, as well as more severe pathological fibrosis when compared with NC. Treatment of AC could decrease BW, FBG, and 24 h UAE and alleviated kidney damage. Compared with the NC group, expressions of miR-192 and miR-200b were increased, whereas their target proteins (ZEB2 and PTEN) were reduced in the kidneys of DN mice, which further modulated the expression of their downstream proteins PI3K p85α, P-AKT, P-smad3, and COL4 α1; these proteins were increased in the kidneys of DN mice. In contrast, AC treatment reversed the expression changes of these proteins. These findings demonstrate that AC may protect the kidneys of DN mice by decreasing miR-192 and miR-200b, which could further regulate their target gene expression and modulate the activity of the PTEN/PI3K/AKT pathway to reduce the degree of renal fibrosis.

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Section: Introductionmentioning

confidence: 99%

The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways

Zhao

Yang

et al. 2019

BioMed Research International

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“…Another study by Murea et al [29] which included a total of 86 biopsy samples from subjects with acquired kidney diseases including DKD and reported found that Notch 1 and Notch 2 are expressed on podocytes in proteinuric nephropathies and their level of expression correlates with the amount of proteinuria (across all disease groups) indicating a possible relation between Notch pathway and renal pathologies other than DKD. Sharaf et al [30] in demonstrated significant positive correlation between Notch 2 expression and albuminuria.…”

Section: Discussionmentioning

confidence: 93%

Expression of Notch 2 and ABCC8 genes in patients with type 2 diabetes mellitus and their association with diabetic kidney disease

Ghanem¹,

Ismail²,

El-Sharkawy³

et al. 2020

Clinical Diabetology

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Background. The incidence of type 2 diabetes mellitus (T2DM) has increased over the past years and early identification and management of its complications especially diabetic kidney disease (DKD) is of great importance. T2DM and DKD are of multifactorial etio logy with contribution of genetic and environmental factors. We aimed to study the expression of ABCC8 and Notch 2 genes in patients with T2DM and to find their association with DKD. Methods. The present work was carried on 80 patients with T2DM (40 with DKD and 40 without DKD) and 40 healthy subjects as a control group. Real time polymerase chain reaction was used to assess gene expression. Results. Altered expression of ABCC8 and Notch 2 genes were found in patients with T2DM compared to control group. ABCC8 expression had significant positive correlation with HbA 1c while Notch 2 expres sion had significant positive correlation with fasting plasma glucose and HbA 1c. Notch 2 expression was significantly higher in patients with DKD compared to those without DKD. Multivariate regression analysis showed that Notch 2 expression had independent relation with increased urinary albumin excretion and reduced estimated glomerular filtration rate. ABCC8 gene expression did not show significant difference between diabetic patients with DKD compared to those without DKD. Conclusion. Increased expression of ABCC8 and Notch 2 genes may play a role in pathogenesis of T2DM. Overexpression of Notch 2 gene may have a role in the development of albuminuria and DKD in patients with T2DM which may represent a possible diagnostic tool and a possible therapeutic target.

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“…Previous study identified PPARG as a transcription factor modulating DKD target genes . And Sharaf et al (2018) found that PPARG showed lower expression in DKD patients and the abundance of PPARG were negatively correlated with microalbumin. Nevertheless, few studies have explored the specific role of PPARG in DKD.…”

Section: Discussionmentioning

confidence: 99%

Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease

Yang

Liu

et al. 2022

Front. Pharmacol.

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Danggui-Shaoyao-San (DSS) is one of traditional Chinese medicine, which recently was found to play a protective role in diabetic kidney disease (DKD). However, the pharmacological mechanisms of DSS remain obscure. This study would explore the molecular mechanisms and bioactive ingredients of DSS in the treatment of DKD through network pharmacology. The potential target genes of DKD were obtained through OMIM database, the DigSee database and the DisGeNET database. DSS-related targets were acquired from the BATMAN-TCM database and the STITCH database. The common targets of DSS and DKD were selected for analysis in the STRING database, and the results were imported into Cytoscape to construct a protein-protein interaction network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis and Gene Ontology (GO) enrichment analysis were carried out to further explore the mechanisms of DSS in treating DKD. Molecular docking was conducted to identify the potential interactions between the compounds and the hub genes. Finally, 162 therapeutic targets of DKD and 550 target genes of DSS were obtained from our screening process. Among this, 28 common targets were considered potential therapeutic targets of DSS for treating DKD. Hub signaling pathways including HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, mTOR signaling pathway, and PI3K-Akt signaling pathway may be involved in the treatment of DKD using DSS. Furthermore, TNF and PPARG, and poricoic acid C and stigmasterol were identified as hub genes and main active components in this network, respectively. In this study, DSS appears to treat DKD by multi-targets and multi-pathways such as inflammatory, oxidative stress, autophagy and fibrosis, which provided a novel perspective for further research of DSS for the treatment of DKD.

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Altered expression of WFS1 and NOTCH2 genes associated with diabetic nephropathy in T2DM patients

Cited by 13 publications

References 38 publications

The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways

The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways

Expression of Notch 2 and ABCC8 genes in patients with type 2 diabetes mellitus and their association with diabetic kidney disease

Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease

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