Identification and validation of key genes of Xiaozhengtongluo formula in the treatment of diabetic nephropathy by Mendelian randomization
Abstract
Abstract Background Xiaozhengtongluo formula (XZTL) has a positive effect on the treatment of diabetic nephropathy (DN), but its mechanism is not fully understood. Therefore, it is important to explore the key genes of XZTL in the treatment of DN. Methods Differentially expressed genes (DEGs) between DN and control obtained from GSE96804, drug target genes of XZTL, and disease target genes of DN obtained from public databases were intersected. Genes of intersection were defined as candidate genes. Next, Mendelian randomization (MR) analysis was used to ascertain the causal associations between candidate genes and DN. Afterwards, key genes were confirmed through receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, enrichment analysis, molecular regulatory network analysis, and molecular docking were conducted. Finally, experimental verification of the expression levels of key genes was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Altogether, 29 candidate genes were described and subjected to the MR analysis, and three key genes (APOD, IGFBP3, LPL) were identified. IGFBP3 was risk factor for DN. LPL and APOD were the protective factors of DN. All three key genes were co-enriched in 26 pathways, such as oxidative phosphorylation and heme metabolism. Regulatory networks for key genes included that MIR497HG regulated IGFBP3 by regulating hsa-miR-19a-3p and NEAT1 regulated LPL by…
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