Deficiency of C3a receptor attenuates the development of diabetic nephropathy (Control Group)
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PROVIDER: PRJNA552023 | ENA |
REPOSITORIES: ENA
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Project description:Deficiency of C3a receptor attenuates the development of diabetic nephropathy
| PRJNA552021 | ENA
Project description:Deficiency of C3a receptor attenuates the development of diabetic nephropathy (Diabetic Group)
| PRJNA552022 | ENA
Project description:Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN. The expression of C3aR was examined in the renal specimen of DN patients. Using a C3aR gene knockout mice (C3aR-/-), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a. Compared with normal controls, the renal expression of C3aR was significantly increased in DN patients. C3aR-/- diabetic mice developed less severe diabetic renal damage compared with WT diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T cell adaptive immunity in C3aR-/- diabetic mice compared with WT diabetic mice and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophages infiltration. In vitro study demonstrated C3a can enhance macrophages secreted cytokines which could induce inflammatory responses and differentiation of T cell lineage. In conclusion, C3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T cell adaptive immunity, possibly by influencing macrophages secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.
2020-04-10 | GSE133597 | GEO
Project description:Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN. The expression of C3aR was examined in the renal specimen of DN patients. Using a C3aR gene knockout mice (C3aR-/-), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a. Compared with normal controls, the renal expression of C3aR was significantly increased in DN patients. C3aR-/- diabetic mice developed less severe diabetic renal damage compared with WT diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T cell adaptive immunity in C3aR-/- diabetic mice compared with WT diabetic mice and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophages infiltration. In vitro study demonstrated C3a can enhance macrophages secreted cytokines which could induce inflammatory responses and differentiation of T cell lineage. In conclusion, C3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T cell adaptive immunity, possibly by influencing macrophages secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.
2020-04-10 | GSE133596 | GEO
Project description:ObjectiveDiabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN.Research design and methodsThe expression of C3aR was examined in the renal specimen of patients with DN. Using a C3aR gene knockout mice (C3aR-/-), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a.ResultsCompared with normal controls, the renal expression of C3aR was significantly increased in patients with DN. C3aR-/- diabetic mice developed less severe diabetic renal damage compared with wild-type (WT) diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T-cell adaptive immunity in C3aR-/- diabetic mice compared with WT diabetic mice, and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophage infiltration. In vitro study demonstrated C3a can enhance macrophage-secreted cytokines which could induce inflammatory responses and differentiation of T-cell lineage.ConclusionsC3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T-cell adaptive immunity, possibly by influencing macrophage-secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.
| S-EPMC6861086 | biostudies-literature
Project description:Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy Keywords = Diabetes Keywords = kidney Keywords = glomeruli Keywords: other
2004-04-01 | GSE1009 | GEO
Project description:Accumulating evidence suggests the pathogenic role of immunity and metabolism in diabetic kidney disease (DKD). Herein, we aimed to investigate the effect of complement factor B (CFB) on lipid metabolism in the development of DKD. We found that in patients with diabetic nephropathy (DN), the staining of Bb, CFB, C3a, C5a, and C5b-9 were significantly elevated in renal tubulointerstitium. Cfb knockout diabetic mice had significantly milder tubulointerstitial injury and less ceramide biosynthesis. The in vitro study demonstrated that cytokine secretion, endoplasmic reticulum stress, oxidative stress, and cell apoptosis were ameliorated in siCFB HK-2 cells under high glucose conditions. Exogenous ceramide supplementation attenuated the protective effect of CFB knockdown in HK-2 cells, while inhibiting ceramide synthases (CERS) with fumonisin B1 in CFB-overexpressing cells rescued the cell injury. CFB knockdown could downregulate the expression of NF-κB p65, which initiates the transcription of CERS3. Furthermore, C3 knockdown abolished CFB-mediated cytokine secretion, NF-κB signaling activation, and subsequently ceramide biosynthesis. Thus, CFB deficiency inhibited activation of the complement alternative pathway and attenuated kidney damage in DKD, especially tubulointerstitial injury, via inhibiting the NF-κB signaling pathway, further blocking the transcription of CERS, which regulates the biosynthesis of ceramide. CFB may be a promising therapeutic target of DKD.
2023-02-01 | GSE217153 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-10 | GSE133598 | GEO
Project description:Transcriptional profiling of human PBMCs comparing healthy controls, patients with diabetic nephropathy and patients with ESRD. PBMCs were analyzed as they mediate inflammatory injury. Goal was to determine effects of increasing severity of diabetic nephropathy on global PBMC gene expression. Microarray analysis of PBMCs taken from patients with varying degrees of diabetic nephropathy.
2020-12-01 | GSE142153 | GEO
Project description:diabetes, mouse models, diabetic nephropathy, streptozotocin db/db Keywords: other
2004-01-20 | GSE710 | GEO