Microarray analysis of the effect of dexamethasone on murine cochlear explants

Abstract

Conclusions: The microarray analysis identified 39 genes up- or down-regulated by dexamethasone in the cultured tissue of mice cochlea. Of the eight genes most highly affected, several are suggested to have protective effects in the traumatized inner ear (Fkbp5, Glucocorticoid-induced leucine zipper (Gilz), glutathione peroxidase 3) and for others, a plausible mechanism of action can be offered (claudin 10, glutamate-ammonia ligase). The present data may support the use of dexamethasone to treat acute sensorineural hearing loss. It is warrantable to test these results in the in vivo cochlea.

Objectives: To identify genes whose expression is markedly up- or down-regulated by dexamethasone in the cochlear tissue.

Methods: Murine cochlear tissue was cultured with or without dexamethasone for 48 h in vitro. The gene expression profiles were compared between the dexamethasone-treated and untreated cochlear tissue using a microarray that covers 33 696 transcripts (24 878 genes) of mice and quantitative real-time RT-PCR.

Results: The microarray analysis identified 39 genes that are up- or down-regulated by more than twofold in the presence of dexamethasone in the cochlear culture. Genes up- or down-regulated by at least threefold include Fkbp5, Gilz, glutathione peroxidase 3, claudin 10, glutamate-ammonia ligase, proteoglycan 1, integrin beta-like 1, and alpha subunit of glycoprotein hormone.

Fig. 1. Overall levels of gene expressions in the cochlear culture with or without dexamethasone

The expression levels of the 33,696 transcripts (27,878 genes) were highly correlated between cochlear cultures with or without dexamethasone (r=0.9928).