Vascular smooth muscle cell migration induced by domains of thrombospondin-1 is differentially regulated - 19/10/11
Corresponding author. Tel.: 315-464-6241; fax: 315-464-6238Abstract |
Background |
Thrombospondin-1 (TSP-1) stimulates vascular smooth muscle cell (VSMC) migration via defined intracellular signaling pathways. The aim of this study was to examine the signaling pathways whereby TSP-1 folded domains (amino-terminal [NH2], procollagen homology [PCH], all 3 type 1 repeats [3TSR], and a single recombinant protein containing the 3rd type 2 repeat, the type 3 repeats, and the carboxyl-terminal [E3T3C1]) induce VSMC migration.
Methods |
Quiescent VSMCs were pretreated with serum-free media or inhibitors: PP2 (c-Src), LY294002 (phosphatidylinositol 3-kinase), FPT (Ras), Y27632 (Rho kinase), SB202190 (p38 kinase), and PD98059 (extracellular signal-regulated kinase). Migration induced by serum-free media, TSP-1, NH2, PCH, 3TSR, and E3T3C1 was assessed using a modified Boyden chamber.
Results |
TSP-1, NH2, 3TSR, and E3T3C1 induced VSMC chemotaxis (P < .05), but PCH did not (P > .05). PP2, FPT, SB202190, and PD98059 attenuated chemotaxis stimulated by TSP-1, NH2, 3TSR, and E3T3C1 (P < .05). LY294002 inhibited TSP-1-induced and E3T3C1-induced (P < .05) but not NH2-induced or 3TSR-induced (P > .05) chemotaxis. Y27632 inhibited NH2-induced, 3TSR-induced, and E3T3C1-induced (P < .05) but not TSP-1-induced (P > .05) induced chemotaxis.
Conclusions |
TSP-1 folded domains are differentially dependent on intracellular signaling pathways to induce migration.
El texto completo de este artículo está disponible en PDF.Keywords : Thrombospondin, Migration, Vascular smooth muscle cells, Domains, Fragments
Esquema
| This work was supported by a VA Merit Award. |
Vol 202 - N° 5
P. 553-557 - novembre 2011 Regresar al número
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