Integrated Analysis of Gene Expression and Immune Cell Infiltration Reveals Dysregulated Genes and miRNAs in Acute Kidney Injury

Acute Kidney Injury (AKI) is a multifaceted condition characterised by rapid deterioration of renal function, often precipitated by diverse etiologies. A comprehensive understanding of the molecular underpinnings of AKI is pivotal for identifying potential diagnostic markers and therapeutic targets. This study utilised bioinformatics to elucidate gene expression and immune infiltration in AKI. Publicly available mRNA and miRNA datasets were harnessed to discern differentially expressed genes (DEGs) and miRNAs in AKI. The CIBERSORT algorithm was employed to quantify immune cell infiltration in AKI samples. Functional enrichment analyses were conducted to unravel the implicated biological processes. Furthermore, the expression of identified genes and miRNAs was validated by quantitative real-time PCR in an AKI model. Our study revealed significant dysregulation of three genes (Aspn, Clec2h, Tmigd1) and two miRNAs (mmu-miR-21a-3p, mmu-miR-223-3p) in AKI, each with p < 0.0001. These molecular markers are implicated in immune responses, tissue remodelling, and inflammation. We observed notable disturbances in specific immune cells, including activated and immature dendritic cells, M1 macrophages, and subsets of T cells (Treg, Th1, Th17). These alterations correlated significantly with AKI pathology, with dendritic cells and M1 macrophages showing p < 0.01, and T cell subsets demonstrating p < 0.05. These results highlight the intricate involvement of the immune system in AKI and indicate significant enrichment of pathways related to immune response, inflammation, and tissue remodelling, pointing to their pivotal roles in AKI pathophysiology. Our study underscored the significance of immune cell infiltration and dysregulated gene and miRNA expression in AKI. The identified genes (Clec2h, Aspn, and Tmigd1) and miRNAs (mmu-miR-21a-3p and mmu-miR-223-3p) offer potential diagnostic markers and therapeutic avenues for AKI. Subsequent investigations targeting these genes and miRNAs, along with the elucidated pathways, may augment the clinical management and outcomes for AKI patients.