Specific expression network analysis of diabetic nephropathy kidney tissue revealed key methylated sites

Abstract

Diabetic nephropathy (DN) is one of the most common and serious complication in diabetes patients. However, the evidences of gene regulation mechanism and epigenetic modification with DN remain unclear. Therefore, it is necessary to search regulating genes for early diagnosis on DN. We identified tissue specific genes through mining the gene expression omnibus (GEO) public database, enriched function by gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) analysis, and further compared tissue-specific network. Meanwhile, combining with differentially methylated sites, we explored the association epigenetic modification with the pathogenesis of DN. Glomeruli (Glom) may be the main tissue of signal recognition and tubulointerstitium (Tub) is mainly associated with energy metabolism in the occurrence of DN. By comparing tissue-specific networks between Glom and Tub, we screened 319 genes, which played an important role in multiple tissue on kidney. Among them, ANXA2, UBE2L6, MME, IQGAP, SLC7A7, and PLG played a key role in regulating the incidence of DN. Besides, we also identified 1 up-regulated gene (PIK3C2B) and 39 down-regulated genes (POLR2G, DDB1, and ZNF230, etc.) in the methylated data of Glom specific genes. In the Tub specific expressed genes, we identified two hypo-methylated genes (PPARA and GLS). Tub mainly caused abnormal energy metabolism, and Glom caused the changes in cell connections and histone modification. By analyzing differentially methylated sites and tissue-specific expressed genes, we found the change of methylated status about the core regulating genes may be a potential factor in the pathogenesis of DN.

<p>Interference of Hsa_circ_0003928 Alleviates High Glucose-Induced Cell Apoptosis and Inflammation in HK-2 Cells via miR-151-3p/Anxa2</p>

“… 28 Specific expression network analysis of diabetic nephropathy kidney tissue also suggested that Anxa2 was a key gene during the development of DN. 29 Furthermore, Anxa2 gene silencing was able to alleviate obesity-induced insulin resistance via suppressing the nuclear factor kappa B (NF-κB) signaling pathway. 30 Therefore, Anxa2 possibly exerts its function in inflammatory environment by regulating NF-κB.…”

Network‐based analysis reveals novel gene signatures in the peripheral blood of patients with sporadic nonsyndromic thoracic aortic aneurysm

“…These methods are applied to distinguish candidate biomarkers or therapeutic targets, such as, predicting the prognosis and progression of the renal cancer (Y. Wang et al, ), guiding research on the diagnosis and treatment of diabetic nephropathy (Y. Z. Wang et al, ), identifying a number of genes and modules plays an important role in systemic lupus erythematosus (Yan et al, ), and discovering a gene which may be a potential clinical biomarker of pulmonary arterial hypertension (T. Wang et al, ).…”

Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease

“…Different methylated patterns in key regulatory genes are thought to contribute to the development of DKD and specific enzymes implicated in histones methylation might play a role in diabetic nephropathy ( Figure 3) (Table 1) [60]. This is also the case for other forms of CKD.…”

“…Indeed, increased Trim13 promoter methylation contributed to downregulation of the expression of the E3 ubiquitin ligase TRIM13 in DKD glomeruli, which was associated to increased mesangial collagen synthesis [71]. DNA methylation may also contribute to modulate the expression of TGF-β1-regulated genes involved in the pathogenesis of DKD [60,72]. Indeed, reactive oxygen species (ROS) modulates DNA methylation [73] and through ROS-dependent DNA methylation of the Tgfb1 locus contribute to mesangial fibrosis in DKD [74].…”