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Article

A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations

1
Centre of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
2
Laboratory of Biology, University of Athens School of Medicine, 11527 Athens, Greece
3
Mosaiques Diagnostics GmbH, 30659 Hannover, Germany
4
Institute for Molecular Cardiovascular Research, University Hospital RWTH Aachen, 52074 Aachen, Germany
5
Laboratory of Cell and Gene Therapy, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece
*
Authors to whom correspondence should be addressed.
Current address: Department of Cardiovascular Disease, Nordic Bioscience A/S, DK-2730 Herlev, Denmark.
Int. J. Mol. Sci. 2025, 26(15), 7480; https://doi.org/10.3390/ijms26157480 (registering DOI)
Submission received: 23 June 2025 / Revised: 22 July 2025 / Accepted: 31 July 2025 / Published: 2 August 2025

Abstract

Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (229NGDDGEAGKPGRPGERGPpGp249). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion.
Keywords: cell migration; cell signaling; collagen; matrikine; urinary peptides cell migration; cell signaling; collagen; matrikine; urinary peptides

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MDPI and ACS Style

Devos, H.; Mina, I.K.; Paradeisi, F.; Makridakis, M.; Tserga, A.; Mokou, M.; Zoidakis, J.; Mischak, H.; Vlahou, A.; Latosinska, A.; et al. A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations. Int. J. Mol. Sci. 2025, 26, 7480. https://doi.org/10.3390/ijms26157480

AMA Style

Devos H, Mina IK, Paradeisi F, Makridakis M, Tserga A, Mokou M, Zoidakis J, Mischak H, Vlahou A, Latosinska A, et al. A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations. International Journal of Molecular Sciences. 2025; 26(15):7480. https://doi.org/10.3390/ijms26157480

Chicago/Turabian Style

Devos, Hanne, Ioanna K. Mina, Foteini Paradeisi, Manousos Makridakis, Aggeliki Tserga, Marika Mokou, Jerome Zoidakis, Harald Mischak, Antonia Vlahou, Agnieszka Latosinska, and et al. 2025. "A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations" International Journal of Molecular Sciences 26, no. 15: 7480. https://doi.org/10.3390/ijms26157480

APA Style

Devos, H., Mina, I. K., Paradeisi, F., Makridakis, M., Tserga, A., Mokou, M., Zoidakis, J., Mischak, H., Vlahou, A., Latosinska, A., & Roubelakis, M. G. (2025). A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations. International Journal of Molecular Sciences, 26(15), 7480. https://doi.org/10.3390/ijms26157480

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