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2015 ; 6
(ä): 310
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Dexamethasone increases aquaporin-2 protein expression in ex vivo inner medullary
collecting duct suspensions
#MMPMID26578982
Chen M
; Cai H
; Klein JD
; Laur O
; Chen G
Front Physiol
2015[]; 6
(ä): 310
PMID26578982
show ga
Aquaporin-2 (AQP2) is the vasopressin-regulated water channel that controls renal
water reabsorption and plays an important role in the maintenance of body water
homeostasis. Excessive glucocorticoid as often seen in Cushing's syndrome causes
water retention. However, whether and how glucocorticoid regulates AQP2 remains
unclear. In this study, we examined the direct effect of dexamethasone on AQP2
protein expression and activity. Dexamethasone increased AQP2 protein abundance
in rat inner medullary collecting duct (IMCD) suspensions. This was confirmed in
HEK293 cells transfected with AQP2 cDNA. Cell surface protein biotinylation
showed an increase of dexamethasone-induced cell membrane AQP2 expression and
this effect was blocked by glucocorticoid receptor antagonist RU486.
Functionally, dexamethasone treatment of oocytes injected with an AQP2 cRNA
increased water transport activity as judged by cell rupture time in a
hypo-osmotic solution (66 ± 13 s in dexamethasone vs. 101 ± 11 s in control, n =
15). We further found that dexamethasone treatment reduced AQP2 protein
degradation, which could result in an increase of AQP2 protein. Interestingly,
dexamethasone promoted cell membrane AQP2 moving to less buoyant lipid raft
submicrodomains. Taken together, our data demonstrate that dexamethasone promotes
AQP2 protein expression and increases water permeability mainly via inhibition of
AQP2 protein degradation. The increase in AQP2 activity promotes water
reabsorption, which may contribute to glucocorticoid-induced water retention and
hypertension.