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TANGO1 inhibitors reduce collagen secretion and limit tissue scarring

Author

Listed:
  • Ishier Raote

    (The Barcelona Institute of Science and Technology
    Institut Jacques Monod)

  • Ann-Helen Rosendahl

    (Medical Faculty)

  • Hanna-Maria Häkkinen

    (The Barcelona Institute of Science and Technology)

  • Carina Vibe

    (The Barcelona Institute of Science and Technology
    EMBL Barcelona)

  • Ismail Küçükaylak

    (University of Cologne)

  • Mugdha Sawant

    (Medical Faculty)

  • Lena Keufgens

    (University of Cologne)

  • Pia Frommelt

    (University of Cologne)

  • Kai Halwas

    (University of Cologne)

  • Katrina Broadbent

    (The Barcelona Institute of Science and Technology)

  • Marina Cunquero

    (The Barcelona Institute of Science and Technology)

  • Gustavo Castro

    (The Barcelona Institute of Science and Technology)

  • Marie Villemeur

    (Institut Jacques Monod)

  • Julian Nüchel

    (Max Planck Institute for Biology of Aging)

  • Anna Bornikoel

    (Medical Faculty)

  • Binita Dam

    (Institute for Stem Cell Science and Regenerative Medicine (inStem))

  • Ravindra K. Zirmire

    (Institute for Stem Cell Science and Regenerative Medicine (inStem))

  • Ravi Kiran

    (Institute for Stem Cell Science and Regenerative Medicine (inStem))

  • Carlo Carolis

    (The Barcelona Institute of Science and Technology)

  • Jordi Andilla

    (The Barcelona Institute of Science and Technology)

  • Pablo Loza-Alvarez

    (The Barcelona Institute of Science and Technology)

  • Verena Ruprecht

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF))

  • Colin Jamora

    (Institute for Stem Cell Science and Regenerative Medicine (inStem))

  • Felix Campelo

    (The Barcelona Institute of Science and Technology)

  • Marcus Krüger

    (University of Cologne)

  • Matthias Hammerschmidt

    (University of Cologne
    University of Cologne)

  • Beate Eckes

    (Medical Faculty)

  • Ines Neundorf

    (University of Cologne)

  • Thomas Krieg

    (Medical Faculty
    University of Cologne
    University of Cologne)

  • Vivek Malhotra

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF))

Abstract

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.

Suggested Citation

  • Ishier Raote & Ann-Helen Rosendahl & Hanna-Maria Häkkinen & Carina Vibe & Ismail Küçükaylak & Mugdha Sawant & Lena Keufgens & Pia Frommelt & Kai Halwas & Katrina Broadbent & Marina Cunquero & Gustavo , 2024. "TANGO1 inhibitors reduce collagen secretion and limit tissue scarring," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47004-1
    DOI: 10.1038/s41467-024-47004-1
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    References listed on IDEAS

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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Oliver Arnolds & Raphael Stoll, 2023. "Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Geoffrey C. Gurtner & Sabine Werner & Yann Barrandon & Michael T. Longaker, 2008. "Wound repair and regeneration," Nature, Nature, vol. 453(7193), pages 314-321, May.
    4. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    5. Frederic Bard & Laetitia Casano & Arrate Mallabiabarrena & Erin Wallace & Kota Saito & Hitoshi Kitayama & Gianni Guizzunti & Yue Hu & Franz Wendler & Ramanuj DasGupta & Norbert Perrimon & Vivek Malhot, 2006. "Functional genomics reveals genes involved in protein secretion and Golgi organization," Nature, Nature, vol. 439(7076), pages 604-607, February.
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