Identification of key lncRNAs contributing to diabetic nephropathy by gene co-expression network analysis

Abstract

LncRNA is reported to have important role in diabetic nephropathy (DN). Here, we aim to identify key lncRNAs of DN using bioinformatics and systems biological methods. Method: Five microarray data sets from Gene Expression Omnibus (GEO) database were included. Probe sets were re-annotated. In the training set, differential expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was constructed to screen diabetic-related hub genes and reveal their potential biological function. Two more human data sets and mouse data sets were used as validation sets. Results: A total of 424 DEGs, including 10 lncRNAs, were filtered in the training data set. WGCNA and enrichment analysis of hub genes showed that inflammation and metabolic disorders are prominent in DN. Three key lncRNAs (NR_130134.1, NR_029395.1 and NR_038335.1) were identified. These lncRNAs are also differently expressed in another two human data sets. Functional enrichment of the mouse data sets showed consistent changes with that in human, indicating similar changes in gene expression pattern of DN and confirmed confidence of our analysis. Human podocytes and mesangial cells were culture in vitro . QPCR and fluorescence in situ hybridization were taken out to validate the expression and relationship of key lncRNAs and their related mRNAs. Results were also consistent with our analysis. Conclusions: Inflammation and metabolic disorders are prominent in DN. We identify three lncRNAs that are involved in these processes possibly by interacting with co-expressed mRNAs.

LncRNA lnc‐ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR‐486‐5p/NFAT5

“…11,16 One such lncRNA, lnc-ISG20 was documented to exhibit up-regulated expression levels in the glomerular of DN patients, while miR-486-5p was correlated with blood glucose or albuminuria, all of which enable non-coding RNAs to serve as promising biomarkers for DN or renal fibrosis. 7,24 However, the underlying mechanisms of lnc-ISG20 and miR-486-5p in regard to DN remain to be uncovered. In view of this, the current study performed a series of experiments, and our findings demonstrated that lnc-ISG20 was highly expressed in DN patients, and exhibited a close relationship with renal fibrosis.…”

Long Non-Coding RNAs in Kidney Disease

“…As to DN, lncRNA ZEB1-AS1 has been shown to enhance the expression of ZEB1 by promoting H3K4me3 histone modification on its promoter during high glucose treatment with increased ZEB1 exerting an anti-fibrotic role [42]. Importantly, since all of these data were primarily obtained in mouse models, a number of expression screens in DN have been able to show evolutionary conservation of lncRNA modulation in human datasets [43,44,45] indicating the future potential of data obtained in mouse models for the patient setting.…”

miR-107 affects cartilage matrix degradation in the pathogenesis of knee osteoarthritis by regulating caspase-1

“…Its pathological features include degeneration of articular cartilage, synovial inflammatory infiltration and secondary osteophyte formation. Patients with this disease are often accompanied by chronic pain, poor flexion and extension of knee joints, and the late course of the disease can also incur limited range of movement or even disability [3,4]. Currently, the majority of KOA patients are the middle-aged and the elder people.…”