Altered gene expression profile in a rat model of gentamicin-induced ototoxicity and nephrotoxicity, and the potential role of upregulated Ifi44 expression.

Abstract

As demonstrated by Alport syndrome, the co-occurrence of auditory and urinary system malformations, and gentamicin-induced ototoxicity and nephrotoxicity, the ears and kidneys potentially share certain molecular pathways. In the present study, microarray chips were used to analyze the changes in the gene expression profile using a rat model of gentamicin-induced ototoxicity and nephrotoxicity, using rat liver tissue as a control. A number of genes were identified to exhibit similar expression changes in the rat ears and kidney tissues, among which microtubule-associated protein 44 (Ifi44), was selected for further analysis to validate its expression changes and confirm potential involvement in the inflammation process in the disease model. Ifi44 is a member of the type I interferon-inducible gene family. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry were performed; the results demonstrated that more inflammatory cells were present in cochlear and renal parenchyma in gentamycin-induced rats, and Ifi44 expression was increased in these two organs compared with control rats. Taken together, with its role in lupus nephritis and expression in the inner ear, the results suggested that Ifi44 is potentially involved in the inflammation associated with gentamicin-induced ototoxicity and nephrotoxicity. The approach of the current study has also provided a strategy for delineating common pathways shared by organs involved in specific diseases.