title: Dexamethasone (DEX) induces Osmotic stress transcription factor 1 (Ostf1) through the Akt-GSK3β pathway in freshwater Japanese eel gill cell cultures.
abstract: Osmosensing and osmoregulatory processes undertaken in gills of euryhaline fish are coordinated by integrative actions of various signaling molecules/transcriptional factors. Considerable numbers of studies report the hyper- and hypo-osmoregulatory functions of fish gills, by illustrating the process of gill cell remodeling and the modulation of the expression of ion channels/transporters. Comparatively mechanistic information relayed from signal integration to transcriptional regulation in mediating gill cell functions has not yet been elucidated. In this study we demonstrate the functional links from cortisol stimulation, to Akt activation, to the expression of the transcriptional factor, Ostf1. Using the synthetic glucocorticoid receptor agonist, dexamethasone (DEX), Ostf1 expression is found to be activated via glucocorticoid receptor (GR) and mediated by the Akt-GSK3β signaling pathway. Pharmacological experiments using kinase inhibitors reveal that the expression of Ostf1 is negatively regulated by Akt activation. The inhibition of PI3K or Akt activities, by the specific kinase inhibitors (wortmannin, LY294002 or SH6), stimulates Ostf1 expression, while a reduction of GSK3β activity by LiCl reduces Ostf1 expression. Collectively, our report for the first time indicates that DEX can induce Ostf1 via GR, with the involvement of the Akt-GSK3β signaling pathway in primary eel gill cell cultures. The data also suggest that Ostf1 may play different roles in gill cell survival during seawater acclimation.
authors.affiliation: Department of Biology, Hong Kong Baptist University , Kowloon Tong, Hong Kong , China.
authors.forename: S C
authors.initials: SC
authors.lastname: Chow
authors.forename: William K F
authors.initials: WK
authors.lastname: Tse
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
keywords: Akt signaling; Dexamethasone; Eel gill cell culture; GSK3β; Osmotic stress transcription factor 1