title: Hypertonic induction of aquaporin-5 expression through an ERK-dependent pathway.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Hoffert
authors.forename: V
authors.initials: V
authors.lastname: Leitch
authors.forename: P
authors.initials: P
authors.lastname: Agre
authors.forename: L S
authors.initials: LS
authors.lastname: King
mesh_terms: D000818:Animals; D051402:Aquaporin 5; D020346:Aquaporins / Q000235:genetics*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D007765:Lacrimal Apparatus / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000378:metabolism
chemical_list: C496038:Aqp5 protein, mouse; C496040:Aqp5 protein, rat; D051402:Aquaporin 5; D020346:Aquaporins; D005419:Flavonoids; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one