IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35159-8.html
   My bibliography  Save this article

GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression

Author

Listed:
  • Jin Liu

    (Fudan University
    Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences)

  • Lihong Pan

    (National Health Commission
    Chinese Academy of Medical Sciences
    Fudan University)

  • Wenxuan Hong

    (Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences)

  • Siqin Chen

    (National Health Commission
    Chinese Academy of Medical Sciences
    Fudan University)

  • Peiyuan Bai

    (Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences)

  • Wei Luo

    (Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences)

  • Xiaolei Sun

    (Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences)

  • Furong He

    (Xiang’an Hospital of Xiamen University)

  • Xinlin Jia

    (Shanghai Jiao Tong University School of Medicine)

  • Jialiang Cai

    (Fudan University)

  • Yingjie Chen

    (University of Mississippi Medical Center 2500N. State St)

  • Kai Hu

    (Fudan University)

  • Zhenju Song

    (Fudan University)

  • Junbo Ge

    (Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences
    Fudan University)

  • Aijun Sun

    (Fudan University
    Fudan University
    National Health Commission
    Chinese Academy of Medical Sciences)

Abstract

Regulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease. The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we show that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia. GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases.

Suggested Citation

  • Jin Liu & Lihong Pan & Wenxuan Hong & Siqin Chen & Peiyuan Bai & Wei Luo & Xiaolei Sun & Furong He & Xinlin Jia & Jialiang Cai & Yingjie Chen & Kai Hu & Zhenju Song & Junbo Ge & Aijun Sun, 2022. "GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35159-8
    DOI: 10.1038/s41467-022-35159-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35159-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35159-8?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. Ruozhu Zhao & Xin Chen & Weiwei Ma & Jinyu Zhang & Jie Guo & Xiu Zhong & Jiacheng Yao & Jiahui Sun & Julian Rubinfien & Xuyu Zhou & Jianbin Wang & Hai Qi, 2020. "A GPR174–CCL21 module imparts sexual dimorphism to humoral immunity," Nature, Nature, vol. 577(7790), pages 416-420, January.
    2. Michael Koeppen & Jae W. Lee & Seong-Wook Seo & Kelley S. Brodsky & Simone Kreth & Ivana V. Yang & Peter M. Buttrick & Tobias Eckle & Holger K. Eltzschig, 2018. "Hypoxia-inducible factor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia-reperfusion injury," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    3. Minako Ito & Kyoko Komai & Setsuko Mise-Omata & Mana Iizuka-Koga & Yoshiko Noguchi & Taisuke Kondo & Ryota Sakai & Kazuhiko Matsuo & Takashi Nakayama & Osamu Yoshie & Hiroko Nakatsukasa & Shunsuke Chi, 2019. "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery," Nature, Nature, vol. 565(7738), pages 246-250, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yingying Nie & Zeming Qiu & Sijia Chen & Zhao Chen & Xiaocui Song & Yan Ma & Niu Huang & Jason G. Cyster & Sanduo Zheng, 2023. "Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive Gs signaling," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    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. David Alarcón-Alarcón & David Cabañero & Jorge Andrés-López & Magdalena Nikolaeva-Koleva & Simona Giorgi & Gregorio Fernández-Ballester & Asia Fernández-Carvajal & Antonio Ferrer-Montiel, 2022. "TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Bhavana Nayer & Jean L. Tan & Yasmin K. Alshoubaki & Yen-Zhen Lu & Julien M. D. Legrand & Sinnee Lau & Nan Hu & Anthony J. Park & Xiao-Nong Wang & Daniela Amann-Zalcenstein & Peter F. Hickey & Trevor , 2024. "Local administration of regulatory T cells promotes tissue healing," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Rhonda L. McFleder & Anastasiia Makhotkina & Janos Groh & Ursula Keber & Fabian Imdahl & Josefina Peña Mosca & Alina Peteranderl & Jingjing Wu & Sawako Tabuchi & Jan Hoffmann & Ann-Kathrin Karl & Axel, 2023. "Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Stefano Suzzi & Tommaso Croese & Adi Ravid & Or Gold & Abbe R. Clark & Sedi Medina & Daniel Kitsberg & Miriam Adam & Katherine A. Vernon & Eva Kohnert & Inbar Shapira & Sergey Malitsky & Maxim Itkin &, 2023. "N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Mark Walkenhorst & Jana K. Sonner & Nina Meurs & Jan Broder Engler & Simone Bauer & Ingo Winschel & Marcel S. Woo & Lukas Raich & Iris Winkler & Vanessa Vieira & Lisa Unger & Gabriela Salinas & Olivie, 2024. "Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-16, 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:13:y:2022:i:1:d:10.1038_s41467-022-35159-8. 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.