title: Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene.
abstract: Aquaporin-1 (AQP1) is a water channel that is induced by hypertonicity. The present study was undertaken to clarify the osmoregulation mechanism of AQP1 in renal medullary cells. In cultured mouse medullary (mIMCD-3) cells, AQP1 expression was significantly induced by hypertonic treatment with impermeable solutes, whereas urea had no effect on AQP1 expression. This result indicates the requirement of a hypertonic gradient. Hypertonicity activated ERK, p38 kinase, and JNK in mIMCD-3 cells. Furthermore, all three MAPKs were phosphorylated by the upstream activation of MEK1/2, MKK3/6, and MKK4, respectively. The treatments with MEK inhibitor U0126, p38 kinase inhibitor SB203580, and JNK inhibitor SP600125 significantly attenuated hypertonicity-induced AQP1 expression in mIMCD-3 cells. In addition, hypertonicity-induced AQP1 expression was significantly reduced by both the dominant-negative mutants of JNK1- and JNK2-expressing mIMCD-3 cells. NaCl-inducible activity of AQP1 promoter, which contains a hypertonicity response element, was attenuated in the presence of U0126, SB203580, and SP600125 in a dose-dependent manner and was also significantly reduced by the dominant-negative mutants of JNK1 and JNK2. These data demonstrate that the activation of ERK, p38 kinase, and JNK pathways and the hypertonicity response element in the AQP1 promoter are involved in hypertonicity-induced AQP1 expression in mIMCD-3 cells.
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box C281, Denver, CO 80262, USA. Fuminori.Umenishi@UCHSC.edu
authors.forename: Fuminori
authors.initials: F
authors.lastname: Umenishi
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation; D006982:Hypertonic Solutions; D048031:JNK Mitogen-Activated Protein Kinases; D007679:Kidney Medulla / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C496021:Aqp1 protein, mouse; D020346:Aquaporins; D006982:Hypertonic Solutions; D051398:Aquaporin 1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases