Medicine and Health

TANGO1 inhibitors reduce collagen secretion and limit tissue scarring

I. Raote, A. Rosendahl, et al.

Researchers including Ishier Raote and Ann-Helen Rosendahl have developed innovative membrane-permeant peptide inhibitors that target the TANGO1-cTAGE5 interaction, crucial for collagen export. This study uncovers promising strategies to modulate ECM hypersecretion, significantly reducing excessive scarring and fibrosis in zebrafish and human dermal cells.

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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

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