TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport

Keishi Narita, Shohei Sasamoto, Schuichi Koizumi, Shizuka Okazaki, Hideki Nakamura, Takafumi Inoue, Sen Takeda

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    The diffusion of materials from systemic circulation to the central nervous system (CNS) is restricted by the blood-brain barrier (BBB) and the bloodcerebrospinal fluid barrier (BCSFB). Choroid plexus epithelial cells (CPECs) of the brain ventricles constitute the BCSFB and regulate the infiltration of plasma proteins as well as immune cells into the interstitium of the CNS. The barrier function is altered in pathologic conditions. However, the regulatory mechanism of BCSFB is not fully understood. Here, we investigated the function of transient receptor potential vanilloid 4 (TRPV4),a polymodally gated divalent cation channel that is highly expressed in CPECs. TRPV4 was localized broadly on the apical membrane in swine CPECs, in contrast with an intense ciliary localization found on other cell types. Treatment with the TRPV4-specific agonist, GSK1016790A (GSK; EC50 34 nM), induced a robust calcium influx and an immediate serine/threonine protein phosphorylation. The agonist treatment induced a marked decrease in the amount of filamentous actin and disintegrated the cell junctions in 10-20 minutes.Incontrast, inhibitionof the basal TRPV4 activity with the TRPV4-specific antagonist, HC067047 (HC; IC<inf>50</inf> 74 nM), reduced the basolateral-to-apical transport of α-2-macroglobulin (A2M). Overall, this study demonstrated a novel physiologic function of TRPV4 in the regulation of BCSFB permeability.

    Original languageEnglish
    Article number261396
    Pages (from-to)2247-2259
    Number of pages13
    JournalFASEB Journal
    Volume29
    Issue number6
    DOIs
    Publication statusPublished - 2015 Jun 1

    Fingerprint

    Cerebrospinal fluid
    TRPV Cation Channels
    Protein Transport
    Cerebrospinal Fluid
    Blood
    Choroid Plexus
    Proteins
    Fluids
    Epithelial Cells
    Neurology
    Central Nervous System
    Macroglobulins
    Phosphorylation
    Intercellular Junctions
    Divalent Cations
    Threonine
    Blood-Brain Barrier
    Infiltration
    Serine
    Inhibitory Concentration 50

    Keywords

    • Actin
    • Calcium imaging
    • Subcellular localization

    ASJC Scopus subject areas

    • Biochemistry
    • Biotechnology
    • Genetics
    • Molecular Biology

    Cite this

    Narita, K., Sasamoto, S., Koizumi, S., Okazaki, S., Nakamura, H., Inoue, T., & Takeda, S. (2015). TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. FASEB Journal, 29(6), 2247-2259. [261396]. https://doi.org/10.1096/fj.14-261396

    TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. / Narita, Keishi; Sasamoto, Shohei; Koizumi, Schuichi; Okazaki, Shizuka; Nakamura, Hideki; Inoue, Takafumi; Takeda, Sen.

    In: FASEB Journal, Vol. 29, No. 6, 261396, 01.06.2015, p. 2247-2259.

    Research output: Contribution to journalArticle

    Narita, K, Sasamoto, S, Koizumi, S, Okazaki, S, Nakamura, H, Inoue, T & Takeda, S 2015, 'TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport', FASEB Journal, vol. 29, no. 6, 261396, pp. 2247-2259. https://doi.org/10.1096/fj.14-261396
    Narita, Keishi ; Sasamoto, Shohei ; Koizumi, Schuichi ; Okazaki, Shizuka ; Nakamura, Hideki ; Inoue, Takafumi ; Takeda, Sen. / TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. In: FASEB Journal. 2015 ; Vol. 29, No. 6. pp. 2247-2259.
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