Extracellular vesicles stimulate smooth muscle cell migration by presenting collagen VI.

Autor: Kapustin A; School of Cardiovascular and Metabolic Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK, Tel. 020 7848 5221, FAX 020 7848 5193., Tsakali SS; School of Cardiovascular and Metabolic Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK, Tel. 020 7848 5221, FAX 020 7848 5193., Whitehead M; School of Cardiovascular and Metabolic Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK, Tel. 020 7848 5221, FAX 020 7848 5193., Chennell G; Wohl Cellular Imaging Centre, King's College London, 5 Cutcombe Road, London, SE5 9NU., Wu MY; School of Cardiovascular and Metabolic Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK, Tel. 020 7848 5221, FAX 020 7848 5193., Molenaar C; School of Cardiovascular and Metabolic Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK, Tel. 020 7848 5221, FAX 020 7848 5193., Kutikhin A; Laboratory for Molecular, Translational and Digital Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo, 650002, Russian Federation., Bogdanov L; Laboratory for Molecular, Translational and Digital Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo, 650002, Russian Federation., Sinitsky M; Laboratory for Molecular, Translational and Digital Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo, 650002, Russian Federation., Rubina K; Laboratory of Morphogenesis and Tissue Reparation, Faculty of Medicine, Lomonosov Moscow State University, Lomonosovsky av. 27-1, Moscow, 119991, Russia, tel/fax +74959329904., Clayton A; Tissue Microenvironment Research Group, Division of Cancer & Genetics, School of Medicine, Cardiff University, Tenovus Building, Cardiff, UK, CF14 2XN., Verweij FJ; Division of Cell Biology, Neurobiology & Biophysics, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands., Pegtel DM; Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Zingaro S; Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL UK., Lobov A; Laboratory of Regenerative Biomedicine, Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretskiy Prospekt, 194064, St. Petersburg, Russia., Zainullina B; Centre for Molecular and Cell Technologies, Research Park, St. Petersburg State University, 7/9 Universitetskaya Embankment, 199034, St. Petersburg, Russia., Owen D; Institute of Immunology and Immunotherapy, School of Mathematics and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, B15 2TT, UK., Parsons M; Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL UK., Cheney RE; Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Warren D; School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ., Humphries MJ; Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, United Kingdom., Iskratsch T; School of Engineering and Materials Science, Faculty of Science and Engineering, Queen Mary University of London, Engineering Building, Mile End Road, E1 4NS., Holt M; Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., Shanahan CM; School of Cardiovascular and Metabolic Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK, Tel. 020 7848 5221, FAX 020 7848 5193.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 22. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1101/2023.08.17.551257
Abstrakt: The extracellular matrix (ECM) supports blood vessel architecture and functionality and undergoes active remodelling during vascular repair and atherogenesis. Vascular smooth muscle cells (VSMCs) are essential for vessel repair and, via their secretome, are able to invade from the vessel media into the intima to mediate ECM remodelling. Accumulation of fibronectin (FN) is a hallmark of early vascular repair and atherosclerosis and here we show that FN stimulates VSMCs to secrete small extracellular vesicles (sEVs) by activating the β1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. Spatially, sEV were secreted via filopodia-like cellular protrusions at the leading edge of migrating cells. We found that sEVs are trapped by the ECM in vitro and colocalise with FN in symptomatic atherosclerotic plaques in vivo . Functionally, ECM-trapped sEVs induced the formation of focal adhesions (FA) with enhanced pulling forces at the cellular periphery. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI. In vitro assays identified collagen VI as playing the key role in cell adhesion and invasion. Taken together our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collage VI enriched sEVs by VSMCs. These sEVs stimulate migration and invasion by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction forces to enable VSMC movement within the complex vascular ECM network.
Databáze: MEDLINE
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