IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-55295-7.html
   My bibliography  Save this article

Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure

Author

Listed:
  • Rui Wang

    (Tongji University)

  • Youwei Chen

    (Tongji University
    Tongji University)

  • Jiazhen Han

    (Tongji University)

  • Huikang Ye

    (Tongji University)

  • Huiran Yang

    (Tongji University)

  • Qianyan Li

    (Tongji University)

  • Yizhen He

    (Tongji University)

  • Boyu Ma

    (Tongji University)

  • Junjie Zhang

    (Tongji University)

  • Yanli Ge

    (Tongji University)

  • Zhe Wang

    (Tongji University)

  • Bo Sun

    (Tongji University)

  • Huahua Liu

    (Tongji University)

  • Liming Cheng

    (Tongji University
    Tongji University)

  • Zhirong Wang

    (Tongji University)

  • Gufa Lin

    (Tongji University
    Tongji University)

Abstract

Acute liver failure (ALF) is a hepatology emergency with rapid hepatic destruction, multiple organ failures, and high mortality. Despite decades of research, established ALF has minimal therapeutic options. Here, we report that the small bioactive compound SCM-198 increases the survival of male ALF mice to 100%, even administered 24 hours after ALF establishment. We identify adiponectin receptor 2 (AdipoR2) as a selective target of SCM-198, with the AdipoR2 R335 residue being critical for the binding and signaling of SCM-198-AdipoR2 and AdipoR2 Y274 residue serving as a molecular switch for Ca2+ influx. SCM-198-AdipoR2 binding causes Ca2+ influx and elevates the phosphorylation levels of CaMKII and NOS3 in the AdipoR2-CaM-CaMKII-NOS3 complex identified in this study, rapidly inducing nitric oxide production for liver protection in murine ALF. SCM-198 also protects human ESC-derived liver organoids from APAP/TAA injuries. Thus, selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 is a rapid-acting therapeutic strategy for advanced ALF.

Suggested Citation

  • Rui Wang & Youwei Chen & Jiazhen Han & Huikang Ye & Huiran Yang & Qianyan Li & Yizhen He & Boyu Ma & Junjie Zhang & Yanli Ge & Zhe Wang & Bo Sun & Huahua Liu & Liming Cheng & Zhirong Wang & Gufa Lin, 2024. "Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55295-7
    DOI: 10.1038/s41467-024-55295-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-55295-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-55295-7?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:15:y:2024:i:1:d:10.1038_s41467-024-55295-7. 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.