IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12417.html
   My bibliography  Save this article

MURC deficiency in smooth muscle attenuates pulmonary hypertension

Author

Listed:
  • Naohiko Nakanishi

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Takehiro Ogata

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Daisuke Naito

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Kotaro Miyagawa

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Takuya Taniguchi

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Tetsuro Hamaoka

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Naoki Maruyama

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Takeru Kasahara

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Masahiro Nishi

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Satoaki Matoba

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

  • Tomomi Ueyama

    (Graduate School of Medical Science, Kyoto Prefectural University of Medicine)

Abstract

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.

Suggested Citation

  • Naohiko Nakanishi & Takehiro Ogata & Daisuke Naito & Kotaro Miyagawa & Takuya Taniguchi & Tetsuro Hamaoka & Naoki Maruyama & Takeru Kasahara & Masahiro Nishi & Satoaki Matoba & Tomomi Ueyama, 2016. "MURC deficiency in smooth muscle attenuates pulmonary hypertension," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12417
    DOI: 10.1038/ncomms12417
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12417
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12417?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12417. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.