IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52718-3.html
   My bibliography  Save this article

Liver mechanosignaling as a natural anti-hepatitis B virus mechanism

Author

Listed:
  • Jianyu Ye

    (Shanghai Medical College Fudan University
    Fudan University)

  • Fahong Li

    (Shanghai Medical College Fudan University
    Fudan University)

  • Ting Hua

    (Shanghai Medical College Fudan University
    Fudan University)

  • Kewei Ma

    (Shanghai Medical College Fudan University)

  • Jinyu Wang

    (Shanghai Medical College Fudan University
    Fudan University)

  • Zixin Zhao

    (Shanghai Medical College Fudan University)

  • Zhongning Yang

    (Shanghai Medical College Fudan University
    Fudan University)

  • Chen Luo

    (Shanghai Medical College Fudan University
    Fudan University)

  • Ruohan Jia

    (Shanghai Medical College Fudan University
    Fudan University)

  • Yaming Li

    (Shanghai Medical College Fudan University
    Fudan University)

  • Menghan Hao

    (Shanghai Medical College Fudan University
    Fudan University)

  • Jian Wu

    (Shanghai Medical College Fudan University)

  • Mengji Lu

    (University of Duisburg-Essen)

  • Zhenghong Yuan

    (Shanghai Medical College Fudan University
    Fudan University)

  • Jiming Zhang

    (Shanghai Medical College Fudan University
    Fudan University)

  • Jieliang Chen

    (Shanghai Medical College Fudan University
    Fudan University)

Abstract

The mechanisms underlying the natural control of hepatitis B virus (HBV) infection have long been an intriguing question. Given the wide physiological range of liver stiffness and the growing attention to the role of mechanical microenvironment in homeostasis and diseases, we investigated how physical matrix cues impact HBV replication. High matrix stiffness significantly inhibited HBV replication and activated YAP in primary hepatocyte culture system, a key molecule in mechanosignaling. YAP activation notably suppressed HBV transcription and antigen expression. Several YAP-induced genes exhibited strong anti-HBV effects. Single-cell analysis of liver tissue from male individuals with active HBV replication revealed a strong significant negative correlation between YAP signature activation and HBV transcript levels. Intraperitoneal administration of YAP small molecule agonist potently controls HBV in male mouse models. These findings unveil a mechanism that involves the mechanical environment of hepatocytes and YAP to clear hepatotropic viral infection in the liver, providing new perspectives for HBV cure studies and antiviral development.

Suggested Citation

  • Jianyu Ye & Fahong Li & Ting Hua & Kewei Ma & Jinyu Wang & Zixin Zhao & Zhongning Yang & Chen Luo & Ruohan Jia & Yaming Li & Menghan Hao & Jian Wu & Mengji Lu & Zhenghong Yuan & Jiming Zhang & Jielian, 2024. "Liver mechanosignaling as a natural anti-hepatitis B virus mechanism," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52718-3
    DOI: 10.1038/s41467-024-52718-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52718-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52718-3?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
    ---><---

    References listed on IDEAS

    as
    1. Sirio Dupont & Leonardo Morsut & Mariaceleste Aragona & Elena Enzo & Stefano Giulitti & Michelangelo Cordenonsi & Francesca Zanconato & Jimmy Le Digabel & Mattia Forcato & Silvio Bicciato & Nicola Elv, 2011. "Role of YAP/TAZ in mechanotransduction," Nature, Nature, vol. 474(7350), pages 179-183, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Aurore Claude-Taupin & Pierre Isnard & Alessia Bagattin & Nicolas Kuperwasser & Federica Roccio & Biagina Ruscica & Nicolas Goudin & Meriem Garfa-Traoré & Alice Regnier & Lisa Turinsky & Martine Burti, 2023. "The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. María García-García & Sara Sánchez-Perales & Patricia Jarabo & Enrique Calvo & Trevor Huyton & Liran Fu & Sheung Chun Ng & Laura Sotodosos-Alonso & Jesús Vázquez & Sergio Casas-Tintó & Dirk Görlich & , 2022. "Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    3. Joseph G. Kern & Andrew M. Tilston-Lunel & Anthony Federico & Boting Ning & Amy Mueller & Grace B. Peppler & Eleni Stampouloglou & Nan Cheng & Randy L. Johnson & Marc E. Lenburg & Jennifer E. Beane & , 2022. "Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Shuangshuang Wan & Kepeng Wang & Peihong Huang & Xian Guo & Wurui Liu & Yaocheng Li & Jingjing Zhang & Zhiyang Li & Jiacheng Song & Wenjing Yang & Xianzheng Zhang & Xianguang Ding & David Tai Leong & , 2024. "Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Kirstin Meyer & Nicholas C. Lammers & Lukasz J. Bugaj & Hernan G. Garcia & Orion D. Weiner, 2023. "Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Zhao Wang & Jan Lauko & Amanda W. Kijas & Elliot P. Gilbert & Petri Turunen & Ramanathan Yegappan & Dongxiu Zou & Jitendra Mata & Alan E. Rowan, 2023. "Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Zheng Zhang & Baoyong Sha & Lingzhu Zhao & Huan Zhang & Jinteng Feng & Cheng Zhang & Lin Sun & Meiqing Luo & Bin Gao & Hui Guo & Zheng Wang & Feng Xu & Tian Jian Lu & Guy M. Genin & Min Lin, 2022. "Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Sujin Kang & Jaekyung Kim & Areum Park & Minsoo Koh & Wonji Shin & Gayoung Park & Taeyun A. Lee & Hyung Jin Kim & Heonjong Han & Yongbo Kim & Myung Kyung Choi & Jae Hyung Park & Eunhye Lee & Hyun-Soo , 2023. "TRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Rui Li & Jingchen Shao & Young-June Jin & Haruya Kawase & Yu Ting Ong & Kerstin Troidl & Qi Quan & Lei Wang & Remy Bonnavion & Astrid Wietelmann & Francoise Helmbacher & Michael Potente & Johannes Gra, 2023. "Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Cheng-Hai Zhang & Yao Gao & Han-Hwa Hung & Zhu Zhuo & Alan J. Grodzinsky & Andrew B. Lassar, 2022. "Creb5 coordinates synovial joint formation with the genesis of articular cartilage," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Cornelis J. Boogerd & Ilaria Perini & Eirini Kyriakopoulou & Su Ji Han & Phit La & Britt Swaan & Jari B. Berkhout & Danielle Versteeg & Jantine Monshouwer-Kloots & Eva Rooij, 2023. "Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Robin Caire & Estelle Audoux & Mireille Thomas & Elisa Dalix & Aurélien Peyron & Killian Rodriguez & Nicola Pordone & Johann Guillemot & Yann Dickerscheit & Hubert Marotte & François Vandenesch & Fréd, 2022. "YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Abdel Rahman Abdel Fattah & Niko Kolaitis & Katrien Daele & Brian Daza & Andika Gregorius Rustandi & Adrian Ranga, 2023. "Targeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Robin M. Skory & Adam A. Moverley & Goli Ardestani & Yanina Alvarez & Ana Domingo-Muelas & Oz Pomp & Blake Hernandez & Piotr Tetlak & Stephanie Bissiere & Claudio D. Stern & Denny Sakkas & Nicolas Pla, 2023. "The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Jie Fang & Shivendra Singh & Changde Cheng & Sivaraman Natarajan & Heather Sheppard & Ahmed Abu-Zaid & Adam D. Durbin & Ha Won Lee & Qiong Wu & Jacob Steele & Jon P. Connelly & Hongjian Jin & Wenan Ch, 2023. "Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    16. Sefora Conti & Valeria Venturini & Adrià Cañellas-Socias & Carme Cortina & Juan F. Abenza & Camille Stephan-Otto Attolini & Emily Middendorp Guerra & Catherine K. Xu & Jia Hui Li & Leone Rossetti & Gi, 2024. "Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    17. Jimyung Seo & HyunSeok Kim & Kyoung Il Min & Changgon Kim & Yongsoo Kwon & Zhenlong Zheng & Yusung Kim & Hyung-Soon Park & Young Seok Ju & Mi Ryung Roh & Kee Yang Chung & Joon Kim, 2022. "Weight-bearing activity impairs nuclear membrane and genome integrity via YAP activation in plantar melanoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    18. Hiroki Takahashi & Ge Yang & Takeshi Yoneshiro & Yohei Abe & Ryo Ito & Chaoran Yang & Junna Nakazono & Mayumi Okamoto-Katsuyama & Aoi Uchida & Makoto Arai & Hitomi Jin & Hyunmi Choi & Myagmar Tumenjar, 2022. "MYPT1-PP1β phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    19. Hongyu Shen & Xun Huang & Yiheng Zhao & Dongmei Wu & Kaili Xue & Jingfei Yao & Yushuang Wang & Nan Tang & Yifu Qiu, 2022. "The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    20. Melati S. Abdul Halim & Jennifer M. Dyson & Max M. Gong & Moira K. O’Bryan & Reza Nosrati, 2024. "Fallopian tube rheology regulates epithelial cell differentiation and function to enhance cilia formation and coordination," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    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_s41467-024-52718-3. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.