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J Biol Chem, Vol. 275, Issue 12, 9070-9077, March 24, 2000
From the Departments of Aquaporin-5 (AQP5) is a water channel protein
expressed in lung, salivary gland, and lacrimal gland epithelia. Each
of these sites may experience fluctuations in surface liquid
osmolarity; however, osmotic regulation of AQP5 expression has not been
reported. This study demonstrates that AQP5 is induced by hypertonic
stress and that induction requires activation of extracellular
signal-regulated kinase (ERK). Incubation of mouse lung epithelial
cells (MLE-15) in hypertonic medium produced a
dose-dependent increase in AQP5 expression; AQP5 protein
peaked by 24 h and returned to baseline levels within hours of
returning cells to isotonic medium. AQP5 induction was observed only
with relatively impermeable solutes, suggesting an osmotic pressure
gradient is required for induction. ERK was selectively activated in
MLE-15 cells by hypertonic stress, and inhibition of ERK activation
with two distinct mitogen-activated extracellular regulated kinase
kinase (MEK) inhibitors, U0126 and PD98059, blocked AQP5 induction.
AQP5 induction was also observed in the lung, salivary, and lacrimal
glands of hyperosmolar rats, suggesting potential physiologic relevance
for osmotic regulation of AQP5 expression. This report provides the
first example of hypertonic induction of an extrarenal aquaporin, as
well as the first association between mitogen-activated protein kinase
signaling and aquaporin expression.
Hypertonic Induction of Aquaporin-5 Expression through an
ERK-dependent Pathway*
,§, and Biological Chemistry and
§ Medicine, Division of Pulmonary and Critical Care
Medicine, The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205
*
This work was supported by National Institutes of Health
Grants HL33991, HL48268, EY11239 (to P. A.), and HL03797 (to
L. S. K.) and by the Cystic Fibrosis Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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