Role of Dendritic Cell in Diabetic Nephropathy

Kim, Hyun Woo; Kim, Mi‐Yeon; Lee, Hwa-Young; Park, Ho-Young; Jhun, Hyunjhung; Kim, Soohyun

doi:10.3390/ijms22147554

Cited by 19 publications

(9 citation statements)

References 88 publications

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“…Mast cells could promote renal fibrosis and inflammation, and thus implicated in the pathogenesis of DN ( 54 , 55 ). A recent study reported that DC plays an important role in the pathogenesis of DN ( 56 ). Therefore, we speculated the C1 subgroup is more likely to develop advanced DN than the C2 subgroup.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies immune-related gene signatures and subtypes in diabetic nephropathy

Wang

Yan

et al. 2022

Front. Endocrinol.

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BackgroundSystemic inflammation and immune response are involved in the pathogenesis of diabetic nephropathy (DN). However, the specific immune-associated signature during DN development is unclear. Our study aimed to reveal the roles of immune-related genes during DN progression.MethodsThe GSE30529 and GSE30528 datasets were acquired from the Gene Expression Omnibus (GEO) database. Then, the intersection between differentially expressed genes (DEGs) and immune score-related genes (ISRGs) was screened. Subsequently, functional enrichment analyses were performed. The different immune phenotype-related subgroups were finally divided using unsupervised clustering. The core genes were identified by WGCNA and the protein-protein interaction (PPI) network. xCell algorithm was applied to assess the proportion of immune cell infiltration.Results92 immune score-related DEGs (ISRDEGs) were identified, and these genes were enriched in inflammation- and immune-associated pathways. Furthermore, two distinct immune-associated subgroups (C1 and C2) were identified, and the C1 subgroup exhibited activated immune pathways and a higher percentage of immune cells compared to the C2 subgroup. Two core genes (LCK and HCK) were identified and all up-regulated in DN, and the expressions were verified using GSE30122, GSE142025, and GSE104954 datasets. GSEA indicated the core genes were mainly enriched in immune-related pathways. Correlation analysis indicated LCK and HCK expressions were positively correlated with aDC, CD4+ Tem, CD8+T cells, CD8+ Tem, and mast cells.ConclusionsWe identified two immune-related genes and two immune-associated subgroups, which might help to design more precise tailored immunotherapy for DN patients.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies immune-related gene signatures and subtypes in diabetic nephropathy

Wang

Yan

et al. 2022

Front. Endocrinol.

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“…However, all DC subgroups do not cause the same pattern of pathological damage to the kidney, varying according to the type and stage of disease development and the activation of different subgroups of DCs. Transplantation of MSCs (mesenchymal stromal cells) into rats with diabetic nephropathy significantly reduced the levels of CD103+CDC1s, while decreasing the expression of inflammatory factors TNF-alpha and MCP-1, which in turn attenuated renal injury through the inactivation of CD8+ T cells 3 . Kidney-infiltrating CD4+ T cells can stimulate macrophages by producing cytokines such as TNF-alpha.…”

Section: Discussionmentioning

confidence: 99%

“…Glomerular damage is one of the main pathological features of DN. There is considerable evidence that inflammatory responses and infiltrating immune cells play an important role in the pathogenesis of diabetic nephropathy and disease progression through the immune system 3 . In addition, the range of responses generated by inflammation plays a key role in the development and progression of diabetic nephropathy and the modulation of inflammation and associated immune activity is emerging as a therapeutic strategy 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Identification of Ribonuclease 6 as an immunoinflammatory key gene associated with the glomerular injury in diabetic nephropathy

Tongyi

Wang

Zhu

et al. 2022

Sci Rep

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Diabetic nephropathy is one of the major causes of end-stage renal disease, and the pathogenesis of the disease has not been elucidated. While the immunoinflammatory response plays an essential role in the progression of diabetic nephropathy. Glomerular expression dataset in diabetic nephropathy was obtained from the GEO database. Differentially expressed genes were identified and functional enrichment analysis was performed to find genes associated with immunity and inflammation from them. The hub genes of immunoinflammatory were identified using MCODE after establishing the PPI network and gene expression was verified with diabetic nephropathy model rats. Xcell was used to assign immune cells to diabetic nephropathy glomerular samples to detect significant changes in immune cells and to analyze correlations with the hub gene. We found 120 DEGs associated with immunity and inflammation, Ribonuclease 6 was the Hub gene with the highest MCODE score. Xcell analysis revealed significant changes of immune cells in DN glomeruli, including upregulated Activated DCs, Conventional DCs, CD4+ Tem, Epithelial cells, Macrophages, Macrophages M1, and Memory B-cells. RNase6 expression showed the highest positive correlation with Macrophages M1, Activated DCs, and Conventional DCs. We verified through the Nephroseq v5 database that RNase6 expression was elevated in DN glomeruli and negatively correlated with glomerular filtration rate. Animal studies revealed that the kidney of DN model rats showed increased RNase6 expression together with inflammatory factor TNF-alpha and chemokine MCP-1. Our study identified RNase6 as a diagnostic and prognostic biomarker for diabetic nephropathy and found that it may play an essential role in the immunoinflammatory damage to the glomerulus.

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“…T2DM is a serious public health issue with significantly increasing rates across the world. 24 As one of the most significant microvascular complications in diabetic patients, DN is considered a metabolic and hemodynamic glomerular disease initiated by hyperglycemia, 25 and the overproduction of various inflammatory factors is involved in the pathogenesis of DN. 26 The current understanding of diabetes-driven vascular complications as well as therapeutic interventions has arisen from studying disease pathogenesis in animal models.…”

Section: Discussionmentioning

confidence: 99%

TNF-α and IL-1β Promote Renal Podocyte Injury in T2DM Rats by Decreasing Glomerular VEGF/eNOS Expression Levels and Altering Hemodynamic Parameters

Wang¹,

Feng²,

Zhang³

et al. 2022

JIR

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Purpose Diabetic nephropathy (DN) is a serious microvascular complication in those with type 2 diabetes mellitus (T2DM). Evidence confirms that serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the T2DM stage are proposed as prognostic markers for DN development, but it is unclear how they affect renal podocyte-associated nephrin and WT-1 expression. In the presence of podocyte injury, glomerular vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and hemodynamic parameters are dysregulated. The current research aimed to clarify the relationship of TNF-α and IL-1β with podocyte injury by altering VEGF/eNOS expression and hemodynamic parameters. Methods A high-fat diet/streptozotocin-induced DN rat model was established. Serum TNF-α and IL-1β levels were tracked in the pre-T2DM, T2DM and DN stages. In the DN stage, the mRNA and protein expression levels of renal TNF-α, IL-1β, VEGF, eNOS, nephrin and WT-1 were studied. Renal hemodynamic parameters, including peak systolic velocity, end-diastolic flow velocity and mean velocity were measured with a color Doppler ultrasound technique. Results Compared to those in the normal control (CTL) group, serum TNF-α and IL-1β levels increased significantly in the pre-T2DM stage (obesity, insulin resistance and hyperlipidemia), T2DM stage (hyperglycemia) and DN stage (abnormal renal functions) (all: P < 0.05) in the DN group. Serum TNF-α and IL-1β levels in the T2DM stage were significantly higher than those in the pre-T2DM stage (two: P < 0.05). Compared to the CTL group, renal nephrin, WT-1, TNF-α, IL-1β, eNOS and VEGF expression and hemodynamic parameters in the DN stage all showed significant differences separately (all: P < 0.05). Conclusion Increased serum and renal TNF-α and IL-1β levels played important roles in reducing renal nephrin and WT-1 expression levels, which may be related to the fact that the former affected renal VEGF/eNOS expression and blood flow parameters in the DN rats.

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Role of Dendritic Cell in Diabetic Nephropathy

Cited by 19 publications

References 88 publications

Bioinformatics analysis identifies immune-related gene signatures and subtypes in diabetic nephropathy

Bioinformatics analysis identifies immune-related gene signatures and subtypes in diabetic nephropathy

Identification of Ribonuclease 6 as an immunoinflammatory key gene associated with the glomerular injury in diabetic nephropathy

TNF-α and IL-1β Promote Renal Podocyte Injury in T2DM Rats by Decreasing Glomerular VEGF/eNOS Expression Levels and Altering Hemodynamic Parameters

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