IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32855-3.html
   My bibliography  Save this article

The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells

Author

Listed:
  • Elena Astanina

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

  • Gabriella Doronzo

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

  • Davide Corà

    (Università degli Studi del Piemonte Orientale)

  • Francesco Neri

    (University of Torino)

  • Salvatore Oliviero

    (University of Torino)

  • Tullio Genova

    (University of Torino)

  • Federico Mussano

    (University of Torino)

  • Emanuele Middonti

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

  • Edoardo Vallariello

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

  • Chiara Cencioni

    (National Research Council (IASI-CNR))

  • Donatella Valdembri

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

  • Guido Serini

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

  • Federica Limana

    (San Raffaele Open University
    IRCCS San Raffaele Pisana)

  • Eleonora Foglio

    (Technoscience, Parco Scientifico e Tecnologico Pontino)

  • Andrea Ballabio

    (Telethon Institute of Genetics and Medicine (TIGEM)
    Federico II University
    Baylor College of Medicine
    Texas Children’s Hospital)

  • Federico Bussolino

    (University of Torino
    Candiolo Cancer Institute-IRCCS-FPO)

Abstract

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGFβ/Smad pathway repressor. The Tgif1 promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression when Tfeb is overexpressed. Furthermore, Tfeb overexpression in vitro prevents TGFβ-induced EMT, and this effect is abolished by Tgif1 silencing. Tfeb loss of function, similar to that of Tgif1, sensitizes cells to TGFβ, inducing an EMT response to low doses of TGFβ. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide insights into injured heart repair and control of cancer progression.

Suggested Citation

  • Elena Astanina & Gabriella Doronzo & Davide Corà & Francesco Neri & Salvatore Oliviero & Tullio Genova & Federico Mussano & Emanuele Middonti & Edoardo Vallariello & Chiara Cencioni & Donatella Valdem, 2022. "The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32855-3
    DOI: 10.1038/s41467-022-32855-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32855-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32855-3?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. Vincent M. Christoffels & Thomas Grieskamp & Julia Norden & Mathilda T. M. Mommersteeg & Carsten Rudat & Andreas Kispert, 2009. "Tbx18 and the fate of epicardial progenitors," Nature, Nature, vol. 458(7240), pages 8-9, April.
    2. Nunzia Pastore & Tuong Huynh & Niculin J. Herz & Alessia Calcagni’ & Tiemo J. Klisch & Lorenzo Brunetti & Kangho Ho Kim & Marco De Giorgi & Ayrea Hurley & Annamaria Carissimo & Margherita Mutarelli & , 2020. "TFEB regulates murine liver cell fate during development and regeneration," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Chen-Leng Cai & Jody C. Martin & Yunfu Sun & Li Cui & Lianchun Wang & Kunfu Ouyang & Lei Yang & Lei Bu & Xingqun Liang & Xiaoxue Zhang & William B. Stallcup & Christopher P. Denton & Andrew McCulloch , 2008. "A myocardial lineage derives from Tbx18 epicardial cells," Nature, Nature, vol. 454(7200), pages 104-108, July.
    4. Kristy Red-Horse & Hiroo Ueno & Irving L. Weissman & Mark A. Krasnow, 2010. "Coronary arteries form by developmental reprogramming of venous cells," Nature, Nature, vol. 464(7288), pages 549-553, March.
    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. Wei Feng & Abha Bais & Haoting He & Cassandra Rios & Shan Jiang & Juan Xu & Cindy Chang & Dennis Kostka & Guang Li, 2022. "Single-cell transcriptomic analysis identifies murine heart molecular features at embryonic and neonatal stages," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Emmanuel Ekow Asmah & Francis Kwaw Andoh & Edem Titriku, 2020. "Trade misinvoicing effects on tax revenue in sub‐Saharan Africa: The role of tax holidays and regulatory quality," Annals of Public and Cooperative Economics, Wiley Blackwell, vol. 91(4), pages 649-672, December.
    3. Tao Zhuang & Mei-Hua Chen & Ruo-Xi Wu & Jing Wang & Xi-De Hu & Ting Meng & Ai-Hua Wu & Yan Li & Yong-Feng Yang & Yu Lei & Dong-Hua Hu & Yan-Xiu Li & Li Zhang & Ai-Jun Sun & Wei Lu & Guan-Nan Zhang & J, 2024. "ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Mariana A. Branco & Tiago P. Dias & Joaquim M. S. Cabral & Perpetua Pinto-do-Ó & Maria Margarida Diogo, 2022. "Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid," Nature Communications, Nature, vol. 13(1), pages 1-18, 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_s41467-022-32855-3. 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.