Identification of Genes Related to the Early Stage of Angiotensin II-induced Acute Renal Injury by Microarray and Integrated Gene Network Analysis

Abstract

Background/Aims: Angiotensin II (Ang II) mediated signaling plays a key role in the development of chronic kidney damage that contributes to renal fibrosis. However, the gene expression changes regulated by Ang II in the early stage of acute renal injury remain unclear. Methods: C57BL/6 wild-type (WT) mice were injected with Ang II (1500 ng/kg/min) for 1, 3 and 7 days. A time series analysis of microarrays was performed to evaluate Ang II-induced differentially gene expression in the kidneys. The data of gene expression in the kidney was further dissected by ANOVA analysis, gene expression profiles, gene network construction and quantitative real-time RT-PCR. Ang II-induced renal inflammation and fibrosis in mice were confirmed by pathological examination. Results: Our microarray data showed that a total of 1,511 differentially expressed genes were identified in the kidneys at 1, 3 and 7 days after Ang II infusion. These genes function in multiple biological processes, including response to stimuli, immune response, cell adhesion, metabolic process, kidney development, regulation of blood pressure, and ion transport, which may play critical roles in the pathobiology of Ang II-induced acute renal injury at the early stage. Furthermore, among these genes, 20 genes were further selected for final investigation. The dynamic gene network analysis demonstrated that fatty acid binding protein 1 (Fabp1) localized in the core of the network. Conclusions: Our data suggests that genes involved in lipid metabolic process, especially Fabp1, may play a central role in the development of Ang II-induced acute renal injury at the early stage.

Keywords

• Fabp1
• Angiotensin II
• Renal damage
• Microarray
• Gene expression profiles