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GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts.

Publication ,  Journal Article
Yu, L; Moriguchi, T; Souma, T; Takai, J; Satoh, H; Morito, N; Engel, JD; Yamamoto, M
Published in: Mol Cell Biol
June 2014

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.

Duke Scholars

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

June 2014

Volume

34

Issue

11

Start / End Page

1929 / 1941

Location

United States

Related Subject Headings

  • Urine
  • Promoter Regions, Genetic
  • Osmolar Concentration
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Kidney Tubules, Collecting
  • Kidney Medulla
  • Homeostasis
  • Green Fluorescent Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yu, L., Moriguchi, T., Souma, T., Takai, J., Satoh, H., Morito, N., … Yamamoto, M. (2014). GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts. Mol Cell Biol, 34(11), 1929–1941. https://doi.org/10.1128/MCB.01659-13
Yu, Lei, Takashi Moriguchi, Tomokazu Souma, Jun Takai, Hironori Satoh, Naoki Morito, James Douglas Engel, and Masayuki Yamamoto. “GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts.Mol Cell Biol 34, no. 11 (June 2014): 1929–41. https://doi.org/10.1128/MCB.01659-13.
Yu L, Moriguchi T, Souma T, Takai J, Satoh H, Morito N, et al. GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts. Mol Cell Biol. 2014 Jun;34(11):1929–41.
Yu, Lei, et al. “GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts.Mol Cell Biol, vol. 34, no. 11, June 2014, pp. 1929–41. Pubmed, doi:10.1128/MCB.01659-13.
Yu L, Moriguchi T, Souma T, Takai J, Satoh H, Morito N, Engel JD, Yamamoto M. GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts. Mol Cell Biol. 2014 Jun;34(11):1929–1941.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

June 2014

Volume

34

Issue

11

Start / End Page

1929 / 1941

Location

United States

Related Subject Headings

  • Urine
  • Promoter Regions, Genetic
  • Osmolar Concentration
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Kidney Tubules, Collecting
  • Kidney Medulla
  • Homeostasis
  • Green Fluorescent Proteins