title: GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts.
abstract: The transcription factor GATA2 plays pivotal roles in early renal development, but its distribution and physiological functions in adult kidney are largely unknown. We examined the GATA2 expression pattern in the adult kidney by tracing green fluorescent protein (GFP) fluorescence in Gata2(GFP/+) mice that recapitulate endogenous GATA2 expression and found a robust GFP expression specifically in the renal medulla. Upon purification of the GFP-positive cells, we found that collecting duct (CD)-specific markers, including aquaporin 2 (Aqp2), an important channel for water reabsorption from urine, were abundantly expressed. To address the physiological function of GATA2 in the CD cells, we generated renal tubular cell-specific Gata2-deficient mice (Gata2-CKO) by crossing Gata2 floxed mice with inducible Pax8-Cre mice. We found that the Gata2-CKO mice showed a significant decrease in Aqp2 expression. The Gata2-CKO mice exhibited high 24-h urine volume and low urine osmolality, two important signs of diabetes insipidus. We introduced biotin-tagged GATA2 into a mouse CD-derived cell line and conducted chromatin pulldown assays, which revealed direct GATA2 binding to conserved GATA motifs in the Aqp2 promoter region. A luciferase reporter assay using an Aqp2 promoter-reporter showed that GATA2 trans activates Aqp2 through the GATA motifs. These results demonstrate that GATA2 regulates the Aqp2 gene expression in CD cells and contributes to the maintenance of the body water homeostasis.
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Takashi
authors.initials: T
authors.lastname: Moriguchi
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Souma
authors.forename: Jun
authors.initials: J
authors.lastname: Takai
authors.forename: Hironori
authors.initials: H
authors.lastname: Satoh
authors.forename: Naoki
authors.initials: N
authors.lastname: Morito
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics*; D001834:Body Water / Q000378:metabolism*; D002460:Cell Line; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000502:physiology*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006706:Homeostasis / Q000502:physiology; D007679:Kidney Medulla / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009994:Osmolar Concentration; D011401:Promoter Regions, Genetic; D014556:Urine / Q000502:physiology
chemical_list: C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D049452:Green Fluorescent Proteins