title: Signal transduction in matrix contraction and the migration of vascular smooth muscle cells in three-dimensional matrix.
abstract: The interaction of vascular smooth muscle cells (SMCs) and extracellular matrix plays important roles in vascular remodeling. We investigated the signaling pathways involved in SMC-induced matrix contraction and SMC migration in three-dimensional (3D) collagen matrix. Matrix contraction is inhibited by the disruption of actin filaments but not microtubules. Therefore, we investigated the roles of signaling pathways related to actin filaments in matrix contraction. SMC-induced matrix contraction was markedly blocked (-80%) by inhibiting the Rho-p160ROCK pathway and myosin light chain kinase, and was decreased to a lesser extent (30-40%) by a negative mutant of Rac and inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) or p38 mitogen-activated protein kinase (MAPK), but it was not affected by the inhibition of Ras and Cdc42-Wiskott-Aldrich syndrome protein (WASP) pathways. Inhibition of extracellular-signal-regulated kinase (ERK) decreased SMC-induced matrix contraction by only 15%. The migration speed and persistence of SMCs in the 3D matrix were decreased by the inhibition of p160ROCK, PI 3-kinase, p38 MAPK or WASP to different extents, and p160ROCK inhibitor had the strongest inhibitory effect. Our results suggest that the SMC-induced matrix contraction and the migration of SMCs in 3D matrix share some signaling pathways leading to force generation at cell-matrix adhesions and that various signaling pathways have different relative importance in the regulations of these processes in SMCs.
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 92093, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: James Jaehyun
authors.initials: JJ
authors.lastname: Moon
authors.forename: Hui
authors.initials: H
authors.lastname: Miao
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
authors.forename: Benjamin P C
authors.initials: BP
authors.lastname: Chen
authors.forename: Suli
authors.initials: S
authors.lastname: Yuan
authors.forename: Yingli
authors.initials: Y
authors.lastname: Hu
authors.forename: Shunichi
authors.initials: S
authors.lastname: Usami
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000166:cytology; D001798:Blood Proteins / Q000494:pharmacology; D002417:Cattle; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases
chemical_list: D001798:Blood Proteins; D003094:Collagen; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D009219:Myosin-Light-Chain Kinase; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D054460:rho-Associated Kinases