Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy

Abstract

Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs) between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus) database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO) enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap) database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.

Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy

“…However, whether patients with SIgA deposition have similar clinical pathological characteristics to patients with IgA deposition, and whether SIgA has a similar pathogenic role to IgA in IgAN are unknown. Recently, some studies began to explore the abnormal expression of gene in IgAN [14,15]. microRNAs (miRNAs) modulate protein expression by targeting mRNA transcripts and triggering translation repression or RNA degradation [16].…”

Formalin-fixed paraffin-embedded renal biopsy tissues: an underexploited biospecimen resource for gene expression profiling in IgA nephropathy

“…The third aspect is related to the statistical procedure used. Previous microarray gene expression studies on biopsy specimens 17,18,20,34 simply compared the IgAN transcriptome with normal renal tissue. Here, we were able to exclude the transcripts that were common to other non-IgAN because they were automatically filtered out by selecting specific gene sets from the VENN diagram.…”

An integrative systems biology approach for precision medicine in diabetic kidney disease

“…Integration of intrarenal transcriptomic data with patient‐specific non‐invasive molecular profile will allow generation of signatures that reflects individual's kidney progression pathogenesis. Pattern‐matching tools, which have been helpful in understanding disease and advancing the discovery of novel drugs in oncology can be applied to detect similarities among gene expression signatures . The drug‐specific molecular profile with the highest correlation to the patient's molecular profile is hypothesized to be the most appropriate candidate.…”

“…Pattern-matching tools, which have been helpful in understanding disease and advancing the discovery of novel drugs in oncology can be applied to detect similarities among gene expression signatures. [46][47][48][49] The drug-specific molecular profile with the highest correlation to the patient's molecular profile is hypothesized to be the most appropriate candidate. This type of integrative systems biology approach is "the right drug for the right patients" approach physician will need to advance treatment in DKD.…”