Multiple Potential Pathways in Diabetes Revealed by Integrated Transcriptome and Pathway Analyses

Abstract

Abstract Liver damage is a primary complication leading to aggravation of diabetes. Therefore, a better understanding of the biological underpinnings of liver damage and the related signalling pathways might lead to the development of novel biomarkers and targeted therapies. While a multitude of transcriptomic data are currently available for diabetes from several parts of the world, almost no such studies have been performed in patients with diabetes after stem cell therapy. This study aimed to improve the understanding of the altered molecular networks in the liver tissue of diabetic rats after stem cell therapy. We compared liver tissues from eight diabetic rats treated with or without adipose-derived stem cells (ADSCs) and identified 1770 upregulated and 362 downregulated transcripts. Selected genes identified by RNA-Seq were subsequently validated using qRT‒PCR. Differentially expressed (2.0-fold change, adj. p < 0.05) transcripts were subjected to Ingenuity Pathway Analysis, which revealed numerous affected signalling pathways and functional categories. Dual specificity phosphatase 1 (DUSP1) mechanistic networks were activated prominently in liver tissue. Additionally, genes related to liver damage, inflammation, and insulin secretion were markedly enriched in liver tissue. Expression of genes indicative of hepatitis, liver steatosis and liver fibrosis was observed in liver tissue. Our data provide novel insight into the biology of liver damage and suggest common alterations in molecular networks during liver damage in diabetic rats and suggest the need for future development of therapeutic interventions targeting these common signalling pathways.