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Abstract
Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. The study designed membrane-permeant peptide inhibitors targeting the TANGO1-cTAGE5 interaction, crucial for collagen export from the endoplasmic reticulum. These inhibitors reduced TANGO1 and cTAGE5 protein levels, inhibiting ECM component secretion. In zebrafish, this led to altered tissue architecture and reduced scar formation. The inhibitors also reduced ECM protein secretion in human dermal fibroblasts and scleroderma patient cells. Targeted interference of TANGO1-cTAGE5 binding could therapeutically modulate ECM hypersecretion.
Publisher
Nature Communications
Published On
Apr 24, 2024
Authors
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 Castro, Marie Villemeur, Julian Nüchel, Anna Bornikoel, Binita Dam, Ravindra K. Zirmire, Ravi Kiran, Carlo Carolis, Jordi Andilla, Pablo Loza-Álvarez, Verena Ruprecht, Colin Jamora, Felix Campelo, Marcus Krüger, Matthias Hammerschmidt, Beate Eckes, Ines Neundorf, Thomas Krieg, Vivek Malhotra
Tags
extracellular matrix
fibrosis
TANGO1
cTAGE5
collagen export
peptide inhibitors
scarring

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