scholarly journals Identification of hub genes and networks in cisplatin-induced acute kidney injury

2021 ◽  
Author(s):  
Lingyun Yang ◽  
Jinwen Xu ◽  
Xunwei Liu ◽  
Yun Cheng ◽  
Hongxia Zhou ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Health Hazard ◽  
Herbal Medicines ◽  
Kidney Injury ◽  
Hub Genes ◽  
Chinese Herbal Medicines ◽  
Chinese Herbal ◽  
Ppi Networks

Abstract Acute kidney injury induced by cisplatin poses a serious health hazard to patients. Thus, this study was undertaken to elucidate key signaling pathways and hub genes relevant for therapeutic intervention involved in cisplatin-induced acute kidney injury(CI-AKI) by bioinformatics. We identified differentially expressed genes(DEGs) by R language on GSE106993 and GSE153625 datasets, downloaded from Gene Expression Omnibus (GEO). GO enrichment analysis and KEGG analysis were used to identify the main functions of common differential genes. The STRING database was used to construct protein-protein interaction (PPI) networks and hub genes were selected by Cytoscape. TransmiR v2.0 database and miRWalk2.0 database were used to construct transcription factor (TF)/microRNA (miRNA)/mRNA networks. Chinese herbal medicines targeting hub genes were screened by the ETMC database. 817 up-regulated genes and 769 down-regulated genes were obtained in CI-AKI model. Tumor necrosis factor(TNF) signaling pathway, P53 signaling, and metabolic signaling pathway are important pathways in CI-AKI. 8 hub genes were identified through PPI (Trp53、Egf、Stat3、Jun、Casp3、Cdh1、Ptgs2、Cat). We also constructed TF/microRNA/mRNA regulatory networks, including 2 TFs, 4 miRNAs and 214 mRNAs. The results of ETMC database analysis showed that Sang-Ye and Ban-Xia could be used for the treatment of CI-AKI. In this study, we identified 8 hub genes and 3 important signaling pathways in CI-AKI model by bioinformatics analysis, which provide targets for the treatment of CI-AKI. And the two Chinese herbal medicines obtained from our research, Sang-Ye and Ban-Xia, are expected to be used for the treatment of CI-AKI. Meanwhile, the TF/miRNA/mRNA networks we constructed are helpful to the further study of the mechanism of CI-AKI.

scholarly journals Antioxidant and anti-inflammatory effect of ligustilide on sepsis-induced acute kidney injury via TLR4/NF-κB and Nrf2/HO-1 signaling

2021 ◽  
Vol 20 (1) ◽  
pp. 83-87
Author(s):  
Xiumin Yang ◽  
Chencai Qiao ◽  
Chao Zheng ◽  
Qingjun Deng
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Commercial Kits

Purpose: To investigate the protective effect of ligustilide on sepsis-induced acute kidney injury (AKI) and the signaling pathways involved.Methods: Sepsis-induced AKI was established by cecal ligation and puncture (CLP) in mice. Histopathological renal damage was examined using hematoxylin and eosin (H & E) staining while creatinine and cytokines were measured using commercial kits. Protein levels were determined by Western blotting.Results: Vacuoles, dilations, degeneration, and necrosis were observed in CLP mouse kidneys, but these alterations were countered by 20 mg/kg of ligustilide. Serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly increased in CLP mice compared with control. Furthermore, the serum levels of these indicators in serum were lowered by ligustilide (p < 0.01). The expression levels of Toll-like receptor 4 (TLR4) TLR4 and phosphorylated nuclear factor (NF)-κB in CLP mice were also downregulated by ligustilide. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels increased in CLP mice, but were attenuated by ligustilide (p < 0.01). Superoxide dismutase (SOD) and glutathione (GSH) levels decreased in CLP mice but were increased by ligustilide (p < 0.01). Increased expression of Nrf2 and heme oxygenase-1 (HO-1) were observed in CLP mice, and were further enhancced by ligustilide.Conclusion: Ligustilide exerts antioxidant and anti-inflammatory effects on sepsis-induced AKI via TLR4/NF-κB and Nrf2/HO-1 signaling pathways. Keywords: Ligustilide, Sepsis, Acute kidney injury, TLR4/NF-κB signaling pathway, Nrf2/HO-1 signaling pathway

scholarly journals Network-Based Expression Analyses and Experimental Verifications Reveal the Involvement of STUB1 in Acute Kidney Injury

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanting Shi ◽  
Genwen Chen ◽  
Jie Teng
Keyword(s):  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Gene Set Enrichment Analysis ◽  
High Morbidity ◽  
Dependent Manner ◽  
Sequencing Data ◽  
Hub Genes ◽  
Ppi Networks ◽  
Renal Tubular

Acute kidney injury (AKI) is a severe and frequently observed condition associated with high morbidity and mortality. The molecular mechanisms underlying AKI have not been elucidated due to the complexity of the pathophysiological processes. Thus, we investigated the key biological molecules contributing to AKI based on the transcriptome profile. We analyzed the RNA sequencing data from 39 native human renal biopsy samples and 9 reference nephrectomies from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and Gene Ontology (GO) analysis revealed that various GO terms were dysregulated in AKI. Gene set enrichment analysis (GSEA) highlighted dysregulated pathways, including “DNA replication,” “chemokine signaling pathway,” and “metabolic pathways.” Furthermore, the protein-to-protein interaction (PPI) networks of the DEGs were constructed, and the hub genes were identified using Cytoscape. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to validate the DEGs in AKI-related modules. Subsequently, the upregulated hub genes STUB1, SOCS1, and VHL were validated as upregulated in human AKI and a mouse cisplatin-induced AKI model. Moreover, the biological functions of STUB1 were investigated in renal tubular epithelial cells. Cisplatin treatment increased STUB1 expression in a dose-dependent manner at both the mRNA and protein levels. Knockdown of STUB1 by siRNA increased the expression of proapoptotic Bax and cleaved caspase-3 while decreasing antiapoptotic Bcl-2. In addition, silencing STUB1 increased the apoptosis of HK-2 cells and the proinflammatory cytokine production of IL6, TNFα, and IL1β induced by cisplatin. These results indicated that STUB1 may contribute to the initiation and progression of AKI by inducing renal tubular epithelial cell apoptosis and renal inflammation.

scholarly journals DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yinwu Bao ◽  
Mengqiu Bai ◽  
Huanhuan Zhu ◽  
Yuan Yuan ◽  
Ying Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Clinical Samples ◽  
Mice Model ◽  
Expression Levels ◽  
Ppar Signaling

AbstractDemethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

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