Evaluation of the Genetic Association and Expressions of Notch-2 /Jagged-1 in Patients with Type 2 Diabetes Mellitus

Al-Awaida, Wajdy; Hameed, Wasan Sami; Hassany, Haider J Al; Al‐Dabet, Moh’d Mohanad; Al-bawareed, O.A.; Hadi, Najah R.

doi:10.5455/medarh.2021.75.101-108

Cited by 11 publications

(9 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have confirmed the association between the increased Notch 1, 3, and 4 expressions in renal tissue and the development of diabetic nephropathy [ 17 , 42 ]. Moreover, one recent study has defined Notch2 and Jagged1 as possible biomarkers for distinguishing moderate and severe stages of diabetic nephropathy [ 43 ]. Although previous studies strongly support the role of Notch signaling in the development of renal fibrosis, they did not establish the specific ligand and receptor responsible for fibrosis advancement in different pathologies, including DN.…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic Rat Kidneys

Jurić

Racetin

Filipović

et al. 2022

Life

View full text Add to dashboard Cite

Background: The aim of this study was to determine the expression of epithelial to mesenchymal transition (EMT)-related transcription factors Snail, Wnt4, and Notch2 with key roles in renal fibrosis, in different renal areas of diabetic rats: glomeruli (G), proximal and distal convoluted tubules (PCT; DCT). Methods: Male Sprague Dawley rats were instilled with 55 mg/kg streptozotocin (diabetes mellitus type I model, DM group) or citrate buffer (control group). Kidney samples were collected 2 weeks and 2 months after DM induction and processed for immunohistochemistry. Results: Diabetic animals showed higher Wnt4 kidney expression both 2 weeks and 2 months post-DM induction, while Snail expression significantly increased only 2 weeks after DM initiation (p < 0.0001). We determined significantly higher expression of examined EMT-related genes in different kidney regions in diabetic animals compared with controls. The most substantial differences were observed in tubular epithelial cells in the period of 2 weeks after induction, with higher Snail and Wnt4 expression in PCT and increased Snail and Notch2 expression in DCT of diabetic animals (p < 0.0001; p < 0.001). Conclusion: The obtained results point to the EMT-related factors Snail, Wnt4, and Notch2 as a potential contributor to diabetic nephropathy development and progression. Changes in their expression, especially in PCT and DCT, could serve as diagnostic biomarkers for the early stages of DM and might be a promising novel therapeutic target in this condition.

show abstract

Section: Discussionmentioning

confidence: 99%

Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic Rat Kidneys

Jurić

Racetin

Filipović

et al. 2022

Life

View full text Add to dashboard Cite

show abstract

“…CXCL5 has been shown to be activated abortion [56]. [85], NOTCH2 [86], LRP1 [87], CLU (clusterin) [88], FCN1 [89], CDKN1A [90], SMAD3 [91], HLA-E [92], PTPRC (protein tyrosine phosphatase receptor type C) [93], MYH9 [94], JAK3 [95], IL6R [96], TIMP1 [97], DOCK8 [98], TNFRSF1B [99], ITGAL (integrin subunit alpha L) [100], CD47 [101], RARA (retinoic acid receptor alpha) [102], DGKD (diacylglycerol kinase delta) [103], PLEK (pleckstrin) [104], PREX1 [105], BSCL2 [106], PANX1 [107], IRF7 [108] [116] were revealed to be expressed in diabetes mellitus, but these genes might be novel targets for GDM. SIX1 [117], GREM1 [118], GHRHR (growth hormone releasing hormone receptor) [119], GPR37L1 [120], CYP2J2 [121], AQP4 [122], ROS1 [123], LBP (lipopolysaccharide binding protein) [124], SGCD (sarcoglycan delta) [133], PTHLH [134], FAP (fibroblast activation protein alpha) [135], THSD7A [136], SHROOM3 [137], ETV1 [138], CYP24A1 [139], SLIT2 [140], GJC1 [141], PPARGC1A [142], TRPM3 [143], IGF1 [144], TRPV6 [145], TLR3 [146], BMP7 [147], DSG2 [148], POSTN (periostin) [149], ENOX1…”

Section: Discussionmentioning

confidence: 99%

“…Pathways include hemostasis [57], neutrophil degranulation [58], immune system [59] and cytokine signaling in immune system [60] are responsible for progression of GDM. LGR5 [61], GREM1 [62], GLRA3 [63], NEUROD4 [64], CYP2J2 [65], KCNH6 [66], LBP (lipopolysaccharide binding protein) [67], CXCL14 [68], RGN (regucalcin) [69], NPY2R [70], SERPINB13 [71], WNT5A [72], EDA (ectodysplasin A) [73], HSD11B2 [74], ACVR1C [75], NEUROD1 [76], SLIT2 [77], PPARGC1A [78], IGF1 [79], OSR1 [80], CYP46A1 [81], TLR3 [82], BMP7 [83], SELP (selectin P) [84], HLA-A [85], NOTCH2 [86], LRP1 [87], CLU (clusterin) [88], FCN1 [89], CDKN1A [90], SMAD3 [91], HLA-E [92], PTPRC (protein tyrosine phosphatase receptor type C) [93], MYH9 [94], JAK3 [95], IL6R [96], TIMP1 [97], DOCK8 [98], TNFRSF1B [99], ITGAL (integrin subunit alpha L) [100], CD47 [101], RARA (retinoic acid receptor alpha) [102], DGKD (diacylglycerol kinase delta) [103], PLEK (pleckstrin) [104], PREX1 [105], BSCL2 [106], PANX1 [107], IRF7 [108], NOTCH1 [109], STIM1 [110], TRIM13 [111], LRBA (LPS responsive beige-like anchor protein) [112], CXCR4 [113], MDM4 [114], MYO9B [115] and PDE5A [116] were revealed to be expressed in diabetes mellitus, but these genes might be novel targets for GDM. SIX1 [117], GREM1 [118], GHRHR (growth hormone releasing hormone receptor) [119], GPR37L1 [120], CYP2J2 [121], AQP4 [122], ROS1 [123], LBP (lipopolysaccharide binding protein) [124], SGCD (sarcoglycan delta) [125], CXCL14 [126], RGN...…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

View full text Add to dashboard Cite

Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy. Numerous biomarkers have been identified that are linked with the occurrence and development of GDM. The aim of this investigation was to identify differentially expressed genes (DEGs) in GDM using a bioinformatics approach to elucidate their molecular pathogenesis. GDM associated expression profiling by high throughput sequencing dataset (GSE154377) was obtained from Gene Expression Omnibus (GEO) database including 28 normal pregnancy samples and 33 GDM samples. DEGs were identified using DESeq2. The gene ontology (GO) and REACTOME pathway enrichments of DEGs were performed by g:Profiler. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into modules using the PEWCC1 algorithm. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were performed with the miRNet database and NetworkAnalyst database. Receiver Operating Characteristic (ROC) analyses was conducted to validate the hub genes. A total of 953 DEGs were identified, of which 478 DEGs were up regulated and 475 DEGs were down regulated. Furthermore, GO and REACTOME pathway enrichment analysis demonstrated that these DEGs were mainly enriched in multicellular organismal process, cell activation, formation of the cornified envelope and hemostasis. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB were identified as key genes in the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB in GDM were validated using ROC analysis. This investigation provides further insights into the molecular pathogenesis of GDM, which might facilitate the diagnosis and treatment of GDM.

show abstract

“…In DKD, the Notch signaling pathway is significantly activated, mediating glomerular function, podocyte damage, and tubular interstitial fibrosis ( Zhang et al, 2021 ; Li et al, 2022 ). A randomized controlled clinical study showed that elevated Notch2 and Jagged1 gene expression levels were associated with DKD in humans and could serve as potential biomarkers for DKD ( Al-Awaida et al, 2021 ). In a study of renal biopsies in patients with DKD and animal models of DKD, it was found that interaction of the Notch signaling pathway with the NF-κB signaling pathway in macrophages promoted polarization of the macrophages and exacerbated the inflammatory response, fibrosis, and necrosis of the intrinsic cells in the kidneys.…”

Section: Specific Cell Types and Associated Signaling Pathways For Dkdmentioning

confidence: 99%

Single-cell transcriptomics: A new tool for studying diabetic kidney disease

et al. 2023

View full text Add to dashboard Cite

The kidney is a complex organ comprising various functional partitions and special cell types that play important roles in maintaining homeostasis in the body. Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and is an independent risk factor for cardiovascular diseases. Owing to the complexity and heterogeneity of kidney structure and function, the mechanism of DKD development has not been fully elucidated. Single-cell sequencing, including transcriptomics, epigenetics, metabolomics, and proteomics etc., is a powerful technology that enables the analysis of specific cell types and states, specifically expressed genes or pathways, cell differentiation trajectories, intercellular communication, and regulation or co-expression of genes in various diseases. Compared with other omics, RNA sequencing is a more developed technique with higher utilization of tissues or samples. This article reviewed the application of single-cell transcriptomics in the field of DKD and highlighted the key signaling pathways in specific tissues or cell types involved in the occurrence and development of DKD. The comprehensive understanding of single-cell transcriptomics through single-cell RNA-seq and single-nucleus RNA-seq will provide us new insights into the pathogenesis and treatment strategy of various diseases including DKD.

show abstract

Evaluation of the Genetic Association and Expressions of Notch-2 /Jagged-1 in Patients with Type 2 Diabetes Mellitus

Cited by 11 publications

References 44 publications

Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic Rat Kidneys

Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic Rat Kidneys

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

Single-cell transcriptomics: A new tool for studying diabetic kidney disease

Contact Info

Product

Resources

About