| Popis: |
Introduction IgA nephropathy (IgAN) is a leading cause of end-stage kidney disease worldwide. It is still challenging to assess the treatment effects of frequently used IgAN drugs. Methods We collected gene-expression profiles of renal tissues from eligible IgAN studies in Gene Expression Omnibus (GEO) dataset. The IgAN drugs were identified by InChIKey from Connectivity Map (CMap) L1000 to construct a reference dataset of perturbational signatures. Dr Insight method of gene-expression connectivity analysis was performed to find effective drugs. Then, potential molecular mechanisms and target genes were explored using bioinformatic methods to assess the robustness of these results. Results Six eligible IgAN studies were collected from GEO, and 92 compounds of drugs were identified from CMap L1000. Four types of calcium channel blockers and two glucocorticoids were identified as the most negatively connected to IgAN. The biological processes of mitosis and response to stimulus were enriched for involvement in the kidney injury of IgAN, and SMC4, TIPARP, TSC22D3, and ZFP36, were the important targets in the process. Conclusions Our results indicated that gene-expression connectivity analysis was useful for evaluating the treatment effects of IgAN drugs, and more attention should be paid to SMC4, TIPARP, TSC22D3, and ZFP36 genes in IgAN. |
