Study on Cardiac Transcriptomic Changes and Inflammatory Responses Induced by Acute Kidney Injury in a Cardiorenal Syndrome Model

Abstract

Cardiorenal syndrome (CRS) is a multifaceted relationship between the heart and kidney, where acute kidneys injury (AKI) directly contributes to cardiac dysfunction. The present study aimed to explore the changes of early transcriptome in heart exposed AKI via a mouse unilateral ureteral obstruction (UUO) model. This study was designed to extract differentially expressed genes (DEGs) and their implicated biological processes as well as pathways from the GSE235751 dataset of high-throughput gene expression profile via bioinformatics tools. Preprocessing-introduction of Data was undergone for data integrity and quality check, Differential expression analysis that identified significant gene expressions changes in heart tissue associated with AKI. Pathway analysis and functional annotation revealed involvement of inflammation, cardiac repair, mitochondrial function and autophagy as the major pathways influencing differences in gene expression. Between unrelated groups, validation of distinctly expressed genes was performed using Principal Component Analysis (PCA) and t-Distributed Stochastic Neighbor Embedding (t-SNE). Gene Set Enrichment Analysis (GSEA) showed downregulation of mitochondrial oxidative bioenergetics and autophagy, while upregulating cell proliferation inflammation pathways. These results indicate that AKI induces robust changes in cardiac gene expression, affecting many different pathways and provide novel information about the molecular mechanisms underlying CRS. These results identify possible early intervention and therapeutic targets for the better understanding and treatment of CRS.