Background Diabetic kidney disease (DKD) is the leading cause of death in people with type 2 diabetes mellitus (T2DM). The main objective of this study is to find the potential biomarkers for DKD. Materials and Methods Two datasets (GSE86300 and GSE184836) retrieved from Gene Expression Omnibus (GEO) database were used, combined with our RNA sequencing (RNA-seq) results of DKD mice (C57 BLKS-32w db/db) and non-diabetic (db/m) mice for further analysis. After processing the expression matrix of the three sets of data using R software “Limma”, differential expression analysis was performed. The significantly differentially expressed genes (DEGs) (—logFC— > 1, p-value < 0.05) were visualized by heatmaps and volcano plots respectively. Next, the co-expression genes expressed in the three groups of DEGs were obtained by constructing a Venn diagram. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were further analyzed the related functions and enrichment pathways of these co-expression genes. Then, qRT-PCR was used to verify the expression levels of co-expression genes in the kidney of DKD and control mice. Finally, protein-protein interaction network (PPI), GO, KEGG analysis and Pearson correlation test were performed on the experimentally validated genes, in order to clarify the possible mechanism of them in DKD. Results Our RNA-seq results identified a total of 125 DEGs, including 59 up-regulated and 66 down-regulated DEGs. At the same time, 183 up-regulated and 153 down-regulated DEGs were obtained in GEO database GSE86300, and 76 up-regulated and 117 down-regulated DEGs were obtained in GSE184836. Venn diagram showed that 13 co-expression DEGs among the three groups of DEGs. GO analysis showed that biological processes (BP) were mainly enriched inresponse to stilbenoid, response to fatty acid, response to nutrient, positive regulation of macrophage derived foam cell differentiation, triglyceride metabolic process. KEGG pathway analysis showed that the three major enriched pathways were cholesterol metabolism, drug metabolism–cytochrome P450, PPAR signaling pathway. After qRT-PCR validation, we obtained 11 genes that were significant differentially expressed in the kidney tissues of DKD mice compared with control mice. (The mRNA expression levels of Aacs, Cpe, Cd36, Slc22a7, Slc1a4, Lpl, Cyp7b1, Akr1c14 and Apoh were declined, whereas Abcc4 and Gsta2 were elevated). Conclusion Our study, based on RNA-seq results, GEO databases and qRT-PCR, identified 11 significant dysregulated DEGs, which play an important role in lipid metabolism and the PPAR signaling pathway, which provide novel targets for diagnosis and treatment of DKD.
Background: Chronic kidney disease (CKD) is a serious threat to human health worldwide, and its incidence is increasing annually. The incidence of CKD is a worldwide problem that heavily threatens human health and is increasing annually. A growing amount of information is emerging about the role of miRNAs in the regulation of renal fibrosis, which has aroused interest in the development of drugs that block pathogenic miRNAs or restore protective miRNAs levels. Methods: The aim of this study was to identify the microRNAs (miRNAs) differentially expressed in renal tissues from patients with progressive DN and FSGS of high fibrosis scores to investigate the function and mechanism of miRNAs in renal fibrosis by using kidney tissues from normal and MCD patients as controls. First, we investigated the expression profiles of miRNAs in human kidney biopsy samples using microarray. Then, two new miRNAs were selected to explore the biological functions in TGF-β1 or HG -induced cell models using human proximal renal tubule cells (HK-2). GO and KEGG Pathway Enrichment Analysis were used to explore the target genes and their mechanism in renal fibrosis. Results: The kidney biopsy samples from three types of diseases representing different fibrosis states, two novel miRNAs, hsa-miR-1470-3p and hsa-miR-4483-3p, were detected as consistently differentially expressed among all three types of patient's renal samples and in mice model. In vitro, hsa-miR-4483-3p was suppressed, whereas hsa-miR-1470-3p was induced by treatment with TGF-β1 or HG. Inhibition of hsa-miR-1470-3p or overexpression of hsa-miR-4483-3p promoted HG or TGF-β1-induced fibrosis in HK-2 cells. The further study revealed that MMP-13 and TIMP1 were the target genes of hsa-miR-1470-3p and hsa-miR-4483-3p, respectively. Conclusion: In conclusion, the present study identifies newly dysregulated miRNA profiles related to fibrosis kidneys. Hsa-miR-1470-3p and hsa-miR-4483-3p are demonstrated to involve in kidney fibrosis by regulation of MMP13, TIMP1 respectively. Our results may represent a promising research direction for renal disorders and help identify new biomarkers and therapeutic targets for chronic kidney disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.