The crosstalk of hedgehog, PI3K and Wnt pathways in diabetes

Benchoula, Khaled; Parhar, Ishwar S.; Wong, Eng Hwa

doi:10.1016/j.abb.2020.108743

Cited by 19 publications

(10 citation statements)

References 66 publications

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“…The above facts are highly consistent with the formation of extracellular traps of neutrophils analyzed in this study. A number of studies have confirmed that signaling pathways, such as Rap1, NF-κB and NOD, are involved in the pathogenesis of DR and DME and are crucial in disease formation ( 59 – 61 ); others have confirmed that in the formation of DR and DME, signaling pathways like hedgehog, PI3K and Wnt even have crosstalk mechanism ( 62 ). Our study reveals the possible signaling pathways related to Th17 cell infiltration and DME formation, which provides a basis for follow-up research.…”

Section: Discussionmentioning

confidence: 99%

Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis and In Vivo Validation

Jing

Zhou

2022

Front. Immunol.

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BackgroundPrevious studies have shown that T-helper 17 (Th17) cell-related cytokines are significantly increased in the vitreous of proliferative diabetic retinopathy (PDR), suggesting that Th17 cells play an important role in the inflammatory response of diabetic retinopathy (DR), but its cell infiltration and gene correlation in the retina of DR, especially in diabetic macular edema (DME), have not been studied.MethodsThe dataset GSE160306 was downloaded from the Gene Expression Omnibus (GEO) database, which contains 9 NPDR samples and 10 DME samples. ImmuCellAI algorithm was used to estimate the abundance of Th17 cells in 24 kinds of infiltrating immune cells. The differentially expressed Th17 related genes (DETh17RGs) between NPDR and DME were documented by difference analysis and correlation analysis. Through aggregate analyses such as gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis, a protein-protein interaction (PPI) network was constructed to analyze the potential function of DETh17RGs. CytoHubba plug-in algorithm, Lasso regression analysis and support vector machine recursive feature elimination (SVM-RFE) were implemented to comprehensively identify Hub DETh17RGs. The expression archetypes of Hub DETh17RGs were further verified in several other independent datasets related to DR. The Th17RG score was defined as the genetic characterization of six Hub DETh17RGs using the GSVA sample score method, which was used to distinguish early and advanced diabetic nephropathy (DN) as well as normal and diabetic nephropathy. Finally, real-time quantitative PCR (qPCR) was implemented to verify the transcription levels of Hub DETh17RGs in the STZ-induced DR model mice (C57BL/6J).Results238 DETh17RGs were identified, of which 212 genes were positively correlated while only 26 genes were negatively correlated. Six genes (CD44, CDC42, TIMP1, BMP7, RHOC, FLT1) were identified as Hub DETh17RGs. Because DR and DN have a strong correlation in clinical practice, the verification of multiple independent datasets related to DR and DN proved that Hub DETh17RGs can not only distinguish PDR patients from normal people, but also distinguish DN patients from normal people. It can also identify the initial and advanced stages of the two diseases (NPDR vs DME, Early DN vs Advanced DN). Except for CDC42 and TIMP1, the qPCR transcription levels and trends of other Hub DETh17RGs in STZ-induced DR model mice were consistent with the human transcriptome level in this study.ConclusionThis study will improve our understanding of Th17 cell-related molecular mechanisms in the progression of DME. At the same time, it also provides an updated basis for the molecular mechanism of Th17 cell crosstalk in the eye and kidney in diabetes.

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Section: Discussionmentioning

confidence: 99%

Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis and In Vivo Validation

Jing

Zhou

2022

Front. Immunol.

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“…found that exosomes from autologous skin fibroblasts promote diabetic skin wound healing through the Akt/β-catenin pathway ( 19 ). There is functional crosstalk between different biological pathways that closely related with diabetes ( 20 ).In order to further understanding the functional roles of lncRNA in the pathological mechanism of type 1 diabetes, we dissected the functional crosstalk between these pathways that enriched by mRNAs in ceRNA networks ( Figure 2D ). In the crosstalk network, two pathways are connected by an edge if they shared at least one gene.…”

Section: Resultsmentioning

confidence: 99%

“…Zhu et al demonstrated in vivo and in vitro that exosomes from macrophages treated with high glucose activate glomerular mesangial cells through the TGF-b1/Smad3 pathway (17).Another important study revealed that mesenchymal stem cell-derived exosomes ameliorated diabetes-induced myocardial injury and fibrosis by inhibiting TGF-b1/Smad2 signaling pathway (18).In addition, Han et al found that exosomes from autologous skin fibroblasts promote diabetic skin wound healing through the Akt/b-catenin pathway (19). There is functional crosstalk between different biological pathways that closely related with diabetes (20).In order to further understanding the functional roles of lncRNA in the pathological mechanism of type 1 diabetes, we dissected the functional crosstalk between these pathways that enriched by mRNAs in ceRNA networks (Figure 2D). In the crosstalk network, two pathways are connected by an edge if they shared at least one gene.…”

Section: Functional Analysis Of Competitively Regulated Mrnasmentioning

confidence: 99%

Dissecting lncRNA-mRNA competitive regulatory network in human islet tissue exosomes of a type 1 diabetes model reveals exosome miRNA markers

Tian¹,

Xue²,

Wu³

et al. 2022

Front. Endocrinol.

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BackgroundEmerging evidence shows that exosomes play a crucial role in the occurrence and development of diabetes and its complications. The molecules in exosomes can be regarded as important markers for the diagnosis of diseases. However, it is presently unclear the pathological association mechanism between exosomes and diabetes.ResultsIn this study, transcriptome data and lncRNA regulatory association data of human pancreatic islet-derived exosome were integrated to construct the ceRNA network. Network analysis revealed that lncRNA with differential expression were primarily involved in islet insulin secretion signaling pathways, including Hippo, TGF-beta, Wnt, FOXO, Neurotrophin and ErbB signaling pathway. Further, combined with miRNA mediated competitive regulation and differential expression analysis results, potential markers of diabetes were revealed and validated in independent datasets. Finally, we analyzed the mechanisms of diabetes based on the competitive regulatory association and function of lncRNA.ConclusionOur results suggest that lncRNA such as lncRNA PVT1, LINC00960 and hsa-miR-107 might be involved in inflammation response in T1DM, and the former lncRNA chose in the present study may serve as novel biomarkers and potential targets for the diagnosis and treatment of T1DM.

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“…SMO (smoothened, frizzled class receptor) is a receptor for hedgehog signaling (Hh signaling) proteins. Hh signaling plays a role in lipid metabolism, insulin sensitivity and inflammatory response [ 54 ]. Moreover, Hh signaling has recently been implicated in the regulation of adipose tissue, and several studies have shown a correlation between the increase in its expression and the increase in body weight and fat mass [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Does Childhood Obesity Trigger Neuroinflammation?

et al. 2022

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Childhood obesity is constantly increasing around the world, and it has become a major public health issue. Considerable evidence indicates that overweight and obesity are important risk factors for the development of comorbidities such as cognitive decline, neuroinflammation and neurodegenerative diseases. It is known that during obesity, adipose tissue undergoes immune, metabolic and functional changes which could induce a neuroinflammatory response of the central nervous system (CNS). In this context, to inspect if obesity can start to trigger the neuroinflammation from a pediatric age, we surgically collected and analyzed adipose tissue from the periumbilical area of three obese children (AT-OB) and two normal-weight children (AT-Ctrl). We considered the transcriptomic profile of our samples to detect alterations in different biological processes that might be also involved in the inflammatory and neuroinflammatory response. Our results show alterations of lipid and fatty acids metabolism in AT-OB compared to the AT-Ctrl. We also observed an onset of inflammatory response in AT-OB. Interestingly, among the genes involved in neuroinflammation, GRN and SMO were upregulated, while IFNGR1 and SNCA were downregulated. Our study highlights that obesity may trigger inflammation and neuroinflammation from a pediatric age.

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The crosstalk of hedgehog, PI3K and Wnt pathways in diabetes

Cited by 19 publications

References 66 publications

Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis and In Vivo Validation

Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis and In Vivo Validation

Dissecting lncRNA-mRNA competitive regulatory network in human islet tissue exosomes of a type 1 diabetes model reveals exosome miRNA markers

Does Childhood Obesity Trigger Neuroinflammation?

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