Effects of extracellular matrix on phenotype modulation and MAPK transduction of rat aortic smooth muscle cells in vitro

Exp Mol Pathol. 2000 Oct;69(2):79-90. doi: 10.1006/exmp.2000.2321.

Abstract

The transition of arterial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype may play an essential role in the formation of atherosclerotic and restenotic lesions. This process includes a prominent structural reorganization and allows cells to acquire the ability to migrate, proliferate, and secrete extracellular matrix components. According to Western blotting analysis and immunohistochemical and morphological observations, laminin not only retains SMCs in a contractile state but also possibly stimulates cells to transform a synthetic to a contractile phenotype at an early stage, mediated by P38 MAPK signal transduction. However, fibronectin promotes SMCs to transform from a contractile to a synthetic phenotype, mediated by the ERK MAPK signal pathway. The localization of smooth muscle alpha -actin, myosin heavy chain isoform SM2, and vimentin in explant-isolated rat SMCs was affected by a substrate of fibronectin and laminin and also by ERK MAP kinase inhibitor (PD098059) and P38 MAPK inhibitor (SB203580). Furthermore, vimentin may play a much more important role in differentiation than desmin in phenotype modulation in rat aortic smooth muscle cells.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Extracellular Matrix / metabolism*
  • Fibronectins / metabolism
  • Flavonoids / pharmacology
  • Laminin / metabolism
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Myosin Heavy Chains / metabolism
  • Phenotype
  • Rats
  • Signal Transduction
  • Vimentin / metabolism
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Actins
  • Enzyme Inhibitors
  • Fibronectins
  • Flavonoids
  • Laminin
  • Vimentin
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Myosin Heavy Chains
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one