Signal transduction in matrix contraction and the migration of vascular smooth muscle cells in three-dimensional matrix

Song Li, James Jaehyun Moon, Hui Miao, Gang Jin, Benjamin P C Chen, Suli Yuan, Yingli Hu, Shunichi Usami, Shu Chien

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)378-388
Number of pages11
JournalJournal of Vascular Research
Volume40
Issue number4
DOIs
StatePublished - 2003

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Keywords

  • Extracellular matrix
  • Force generation
  • Migration
  • Rho
  • Signal transduction
  • Smooth muscle cells
  • Three-dimensional matrix

ASJC Scopus subject areas

  • Physiology

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