Fibronectin matrix polymerization regulates smooth muscle cell phenotype through a Rac1 dependent mechanism

Feng Shi, Xiaochun Long, Allison Hendershot, Joseph M. Miano, Jane Sottile

Research output: Contribution to journalArticle

Abstract

Smooth muscle cells are maintained in a differentiated state in the vessel wall, but can be modulated to a synthetic phenotype following injury. Smooth muscle phenotypic modulation is thought to play an important role in the pathology of vascular occlusive diseases. Phenotypically modulated smooth muscle cells exhibit increased proliferative and migratory properties that accompany the downregulation of smooth muscle cell marker proteins. Extracellular matrix proteins, including fibronectin, can regulate the smooth muscle phenotype when used as adhesive substrates. However, cells produce and organize a 3-dimensional fibrillar extracellular matrix, which can affect cell behavior in distinct ways from the protomeric 2-dimensional matrix proteins that are used as adhesive substrates. We previously showed that the deposition/ polymerization of fibronectin into the extracellular matrix can regulate the deposition and organization of other extracellular matrix molecules in vitro. Further, our published data show that the presence of a fibronectin polymerization inhibitor results in increased expression of smooth muscle cell differentiation proteins and inhibits vascular remodeling in vivo. In this manuscript, we used an in vitro cell culture system to determine the mechanism by which fibronectin polymerization affects smooth muscle phenotypic modulation. Our data show that fibronectin polymerization decreases the mRNA levels of multiple smooth muscle differentiation genes, and downregulates the levels of smooth muscle a-actin and calponin proteins by a Rac1-dependent mechanism. The expression of smooth muscle genes is transcriptionally regulated by fibronectin polymerization, as evidenced by the increased activity of luciferase reporter constructs in the presence of a fibronectin polymerization inhibitor. Fibronectin polymerization also promotes smooth muscle cell growth, and decreases the levels of actin stress fibers. These data define a Rac1-dependent pathway wherein fibronectin polymerization promotes the SMC synthetic phenotype by modulating the expression of smooth muscle cell differentiation proteins.

Original languageEnglish (US)
Article numbere94988
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 21 2014
Externally publishedYes

Fingerprint

fibronectins
Fibronectins
Polymerization
polymerization
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
Cells
Phenotype
phenotype
Smooth Muscle
extracellular matrix
Extracellular Matrix
Adhesives
proteins
Actins
Cell Differentiation
Proteins
rac1 GTP-Binding Protein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Fibronectin matrix polymerization regulates smooth muscle cell phenotype through a Rac1 dependent mechanism. / Shi, Feng; Long, Xiaochun; Hendershot, Allison; Miano, Joseph M.; Sottile, Jane.

In: PloS one, Vol. 9, No. 4, e94988, 21.04.2014.

Research output: Contribution to journalArticle

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