Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Matrix-associated extracellular vesicles modulate human smooth muscle cell adhesion and directionality by presenting collagen VI. / Kapustin, AN; Tsakali, SS; Whitehead, M; Chennell, G; Wu, MY; Molenaar, C; Kutikhin, A; Chen, YM; Ahmad, S; Bogdanov, L; Sinitsky, M; Rubina, K; Clayton, A; Verweij, FJ; Pegtel, DM; Zingaro, S; Lobov, A; Zainullina, B; Owen, D; Parsons, M; Cheney, RE; Warren, DT; Humphries, MJ; Iskratsch, T; Holt, M; Shanahan, CM.
в: eLife, Том 12, 2025.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Matrix-associated extracellular vesicles modulate human smooth muscle cell adhesion and directionality by presenting collagen VI
AU - Kapustin, AN
AU - Tsakali, SS
AU - Whitehead, M
AU - Chennell, G
AU - Wu, MY
AU - Molenaar, C
AU - Kutikhin, A
AU - Chen, YM
AU - Ahmad, S
AU - Bogdanov, L
AU - Sinitsky, M
AU - Rubina, K
AU - Clayton, A
AU - Verweij, FJ
AU - Pegtel, DM
AU - Zingaro, S
AU - Lobov, A
AU - Zainullina, B
AU - Owen, D
AU - Parsons, M
AU - Cheney, RE
AU - Warren, DT
AU - Humphries, MJ
AU - Iskratsch, T
AU - Holt, M
AU - Shanahan, CM
N1 - Times Cited in Web of Science Core Collection: 1 Total Times Cited: 1 Cited Reference Count: 111
PY - 2025
Y1 - 2025
N2 - 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, can 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. Here, we show that FN stimulates human VSMCs to secrete small extracellular vesicles (sEVs) by activating the beta 1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. 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 preventing cellular spreading and adhesion. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI on the sEV surface. In vitro assays identified collagen VI as playing a key role in cell adhesion and invasion directionality. Taken together, our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collagen VI enriched sEVs by VSMCs. These sEVs stimulate directional invasion, most likely by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction force to enable VSMC movement within the complex vascular ECM network.
AB - 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, can 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. Here, we show that FN stimulates human VSMCs to secrete small extracellular vesicles (sEVs) by activating the beta 1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. 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 preventing cellular spreading and adhesion. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI on the sEV surface. In vitro assays identified collagen VI as playing a key role in cell adhesion and invasion directionality. Taken together, our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collagen VI enriched sEVs by VSMCs. These sEVs stimulate directional invasion, most likely by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction force to enable VSMC movement within the complex vascular ECM network.
KW - extracellular matrix
KW - cell migration
KW - cell adhesion
KW - regeneration
KW - BINDING PROTEIN RHO
KW - ACTIN STRESS FIBERS
KW - EXOSOME SECRETION
KW - ATHEROSCLEROTIC PLAQUES
KW - VASCULAR CALCIFICATION
KW - AMEBOID INVASIVENESS
KW - MEMBRANE PROTRUSION
KW - FOCAL ADHESIONS
KW - MYOSIN-X
KW - INTEGRIN
U2 - 10.7554/eLife.90375
DO - 10.7554/eLife.90375
M3 - статья
VL - 12
JO - eLife
JF - eLife
SN - 2050-084X
ER -
ID: 147948735