Thyroid transcription factor-1 facilitates cerebrospinal fluid formation by regulating aquaporin-1 synthesis in the brain

Geun Kim Jae, June Son Young, Ho Yun Chang, Il Kim Young, Seong Nam Goong Il, Heon Park Jun, Kyu Park Sang, Sergio R. Ojeda, Angela Valentina D'Elia, Giuseppe Damante, Ju Lee Byung

    Research output: Contribution to journalArticle

    34 Scopus citations

    Abstract

    In the brain, aquaporin-1 (AQP-1), a water channel for high osmotic water permeability, is mainly expressed in the apical membrane of the ventricular choroid plexus and regulates formation of cerebrospinal fluid (CSF). Although the physiology of AQP-1 has been the subject of several publications, much less is known about the trans-acting factors involved in the control of AQP-1 gene expression. Here we report that TTF-1, a homeodomain-containing transcriptional regulator, is coexpressed with AQP-1 in the rat brain choroid plexus and enhances AQP-1 gene transcription by binding to conserved core TTF-1-binding motifs in the 5′-flanking region of the AQP-1 gene. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased AQP-1 synthesis and reduced CSF formation. In addition, blockade of TTF-1 synthesis increased survival of the animals following acute water intoxication-induced brain edema. These results suggest that TTF-1 is physiologically involved in the transcriptional control of AQP-1, which is required for CSF formation.

    Original languageEnglish (US)
    Pages (from-to)14923-14931
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume282
    Issue number20
    DOIs
    StatePublished - May 18 2007

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Jae, G. K., Young, J. S., Chang, H. Y., Young, I. K., Il, S. N. G., Jun, H. P., Sang, K. P., Ojeda, S. R., D'Elia, A. V., Damante, G., & Byung, J. L. (2007). Thyroid transcription factor-1 facilitates cerebrospinal fluid formation by regulating aquaporin-1 synthesis in the brain. Journal of Biological Chemistry, 282(20), 14923-14931. https://doi.org/10.1074/jbc.M701411200