@article {6680,
	title = {TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.},
	journal = {Nat Commun},
	volume = {15},
	year = {2024},
	month = {2024 Apr 24},
	pages = {3302},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Cicatrix, Collagen, Endoplasmic Reticulum, Extracellular Matrix, Fibroblasts, Fibrosis, Humans, Peptides, Scleroderma, Systemic, Skin, Wound Healing, Zebrafish},
	issn = {2041-1723},
	doi = {10.1038/s41467-024-47004-1},
	author = {Raote, Ishier and Rosendahl, Ann-Helen and H{\"a}kkinen, Hanna-Maria and Vibe, Carina and K{\"u}{\c c}{\"u}kaylak, Ismail and Sawant, Mugdha and Keufgens, Lena and Frommelt, Pia and Halwas, Kai and Broadbent, Katrina and Cunquero, Marina and Castro, Gustavo and Villemeur, Marie and N{\"u}chel, Julian and Bornikoel, Anna and Dam, Binita and Zirmire, Ravindra K and Kiran, Ravi and Carolis, Carlo and Andilla, Jordi and Loza-Alvarez, Pablo and Ruprecht, Verena and Jamora, Colin and Campelo, Felix and Kr{\"u}ger, Marcus and Hammerschmidt, Matthias and Eckes, Beate and Neundorf, Ines and Krieg, Thomas and Malhotra, Vivek}
}
