Identification of differentially expressed genes in the endothelial precursor cells of patients with type 2 diabetes mellitus by bioinformatics analysis

Shen, Zhida; Chen, Qi; Ying, Hangying; Ma, Zetao; Bi, Xiwen; Li, Xiaoting; Wang, Meihui; Jin, Chongying; Lai, Dongwu; Zhao, Yanbo; Fu, Guosheng

doi:10.3892/etm.2019.8239

Cited by 11 publications

(10 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies showed elevated circulating IL-8 levels in T2DM patients [193]. A bioinformatic analysis in endothelial precursor cells isolated from patients with T2DM showed that IL-8 and CXCL1 genes were the most expressed molecules in diabetic samples [196].…”

Section: Other Cytokines/proinflammatory Proteins In Dnmentioning

confidence: 95%

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Rayego‐Mateos

Morgado‐Pascual

Opazo-Ríos

et al. 2020

IJMS

188

127

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

show abstract

Section: Other Cytokines/proinflammatory Proteins In Dnmentioning

confidence: 95%

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Rayego‐Mateos

Morgado‐Pascual

Opazo-Ríos

et al. 2020

IJMS

188

127

View full text Add to dashboard Cite

show abstract

“…We completed the network topology analysis with a threshold power ranging from 1 to 20. When the power value was equal to 7 (scale-free R 2 = 0:9) [21], our record showed a scale-free gene coexpression network with complete module characteristics. The cluster tree structure of the topology overlap matrix was constructed.…”

Section: Gene Coexpression Network Of T2dmmentioning

confidence: 84%

“…Weighted correlation network analysis (WGCNA) is a systems biology method to describe the correlation patterns between genes across microarray samples, which is used to find highly related gene modules and calculate module membership to identify candidate biomarkers or 2 BioMed Research International therapeutic targets [20]. This algorithm has been widely used to identify biomarkers at the transcriptional level [21][22][23]. In this study, microarray data from public databases were subjected to WGCNA, and a coexpression network was constructed to screen differential genes between patients with T2DM and healthy people.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Biomarkers of Type 2 Diabetes Mellitus-Related Immune Infiltration Using Weighted Gene Coexpression Network Analysis

Zhang

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Background. Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade inflammation, showing an increasing trend. The infiltration of immune cells into adipose tissue has been shown to be an important pathogenic cause of T2DM. The purpose of this study is to use the relevant database to identify some abnormally expressed or dysfunctional genes related to diabetes from the perspective of immune infiltration. Methods. Weighted gene coexpression network analysis (WGCNA) was employed to systematically identify the coexpressed gene modules and hub genes associated with T2DM development based on a microarray dataset (GSE23561) from the Gene Expression Omnibus (GEO) database. The key genes in modules highly related to clinical features were calculated and screened by using R software, and their participation in T2DM was determined by gene enrichment analysis. The mRNA levels of CSF1R, H2AFV, LCK, and TLR9 in pre-T2DM mice and normal wild-type mice were detected by WGCNA screening and real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results. We constructed 14 coexpressed gene modules, and the brown module was shown to be significantly related to T2DM. Through verification of the protein-protein interaction (PPI) network, four upregulated hub genes, CSF1R, H2AFV, LCK, and TLR9, were screened from the brown module and successfully distinguishedT2DM patients from healthy people. These hub genes may be used as biomarkers and important indicators for patient diagnosis. Enrichment analysis showed that these hub genes were highly associated with IL-6-related inflammatory metabolism, immune regulation, and immune cell infiltration. Finally, we verified the hub genes CSF1R, LCK, and TLR9 in a T2DM animal model and found that their mRNA levels were significantly higher in animals with T2DM than in control group mice (NC). Conclusions. In summary, our results suggest that these hub genes (CSF1R, LCK, and TLR9) can serve as biomarkers and immunotherapeutic targets for T2DM.

show abstract

“…The gene network and pathways were analysed using DAVID v6.8 for GO enrichment analysis with Benjamini significant P < 0.05 for both up‐regulated and down‐regulated genes. The Gene interaction network construction and visualization was performed using Cytoscape v3.8.2 29,30 . The identified treatment responsive differentially expressed genes were created with the Search Tool for the Retrieval of Interacting Genes and proteins (STRING) database.…”

Section: Methodsmentioning

confidence: 99%

Nampt activator P7C3 ameliorates diabetes and improves skeletal muscle function modulating cell metabolism and lipid mediators

Manickam

Tur

Badole

et al. 2022

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Nicotinamide phosphoribosyltransferase (Nampt), a key enzyme in NAD salvage pathway is decreased in metabolic diseases, and its precise role in skeletal muscle function is not known. We tested the hypothesis, Nampt activation by P7C3 (3,6-dibromo-α-[(phenylamino)methyl]-9H-carbazol-9-ethanol) ameliorates diabetes and muscle function. Methods We assessed the functional, morphometric, biochemical, and molecular effects of P7C3 treatment in skeletal muscle of type 2 diabetic (db/db) mice. Nampt +/À mice were utilized to test the specificity of P7C3. Results Insulin resistance increased 1.6-fold in diabetic mice compared with wild-type mice and after 4 weeks treatment with P7C3 rescued diabetes (P < 0.05). In the db-P7C3 mice fasting blood glucose levels decreased to 0.96-fold compared with C57Bl/6J wild-type naïve control mice. The insulin and glucose tolerance tests blood glucose levels were decreased to 0.6-fold and 0.54-folds, respectively, at 120 min along with an increase in insulin secretion (1.76-fold) and pancreatic β-cells (3.92-fold) in db-P7C3 mice. The fore-limb and hind-limb grip strengths were increased to 1.13-fold and 1.17-fold, respectively, together with a 14.2-fold increase in voluntary running wheel distance in db-P7C3 mice. P7C3 treatment resulted in a 1.4-fold and 7.1-fold increase in medium-sized and larger-sized myofibres cross-sectional area, with a concomitant 0.5-fold decrease in smaller-sized myofibres of tibialis anterior (TA) muscle. The transmission electron microscopy images also displayed a 1.67-fold increase in myofibre diameter of extensor digitorum longus muscle along with 2.9-fold decrease in mitochondrial area in db-P7C3 mice compared with db-Veh mice. The number of SDH positive myofibres were increased to 1.74-fold in db-P7C3 TA muscles. The gastrocnemius and TA muscles displayed a decrease in slow oxidative myosin heavy chain type1 (MyHC1) myofibres expression (0.46-fold) and immunostaining (6.4-fold), respectively. qPCR analysis displayed a 2.9-fold and 1.3-fold increase in Pdk4 and Cpt1, and 0.55-fold and 0.59-fold decrease in Fgf21 and 16S in db-P7C3 mice. There was also a 3.3-fold and 1.9-fold increase in Fabp1 and CD36 in db-Veh mice. RNA-seq differential gene expression volcano plot displayed 1415 genes to be up-regulated and 1726 genes down-regulated (P < 0.05) in db-P7C3 mice. There was 1.02-fold increase in serum HDL, and 0.9-fold decrease in low-density lipoprotein/very low-density lipoprotein ratio in db-P7C3 mice. Lipid profiling of gastrocnemius muscle displayed a decrease in inflammatory lipid mediators n-6; AA (0.83-fold), and n-3; DHA (0.69-fold) and EPA (0.81-fold), and a 0.66-fold decrease in endocannabinoid 2-AG and 2.0-fold increase in AEA in db-P7C3 mice. Conclusions Overall, we demonstrate that P7C3 activates Nampt, improves type 2 diabetes and skeletal muscle function in db/db mice.

show abstract

Identification of differentially expressed genes in the endothelial precursor cells of patients with type 2 diabetes mellitus by bioinformatics analysis

Cited by 11 publications

References 59 publications

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Identification of Potential Biomarkers of Type 2 Diabetes Mellitus-Related Immune Infiltration Using Weighted Gene Coexpression Network Analysis

Nampt activator P7C3 ameliorates diabetes and improves skeletal muscle function modulating cell metabolism and lipid mediators

Contact Info

Product

Resources

About