Rho guanine nucleotide exchange factors involved in cyclic-stretch-induced reorientation of vascular endothelial cells

Hiyori Abiko, Sachiko Fujiwara, Kazumasa Ohashi, Ryuichi Hiatari, Toshiya Mashiko, Naoya Sakamoto, Masaaki Sato, Kensaku Mizuno

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Cyclic stretch is an artificial model of mechanical force loading, which induces the reorientation of vascular endothelial cells and their stress fibers in a direction perpendicular to the stretch axis. Rho family GTPases are crucial for cyclic-stretch-induced endothelial cell reorientation; however, the mechanism underlying stretch-induced activation of Rho family GTPases is unknown. A screen of short hairpin RNAs targeting 63 Rho guanine nucleotide exchange factors (Rho-GEFs) revealed that at least 11 Rho-GEFs - Abr, alsin, ARHGEF10, Bcr, GEF-H1 (also known as ARHGEF2), LARG (also known as ARHGEF12), p190RhoGEF (also known as ARHGEF28), PLEKHG1, P-REX2, Solo (also known as ARHGEF40) and α-PIX (also known as ARHGEF6) - which specifically or broadly target RhoA, Rac1 and/or Cdc42, are involved in cyclic-stretch-induced perpendicular reorientation of endothelial cells. Overexpression of Solo induced RhoA activation and F-actin accumulation at cell-cell and cell-substrate adhesion sites. Knockdown of Solo suppressed cyclic-stretch- or tensile-force-induced RhoA activation. Moreover, knockdown of Solo significantly reduced cyclic-stretch-induced perpendicular reorientation of endothelial cells when cells were cultured at high density, but not when they were cultured at low density or pretreated with EGTA or VE-cadherin-targeting small interfering RNAs. These results suggest that Solo is involved in cell-cell-adhesion-mediated mechanical signal transduction during cyclicstretch-induced endothelial cell reorientation.

Original languageEnglish
Pages (from-to)1683-1695
Number of pages13
JournalJournal of cell science
Volume128
Issue number9
DOIs
Publication statusPublished - 2015

Keywords

  • Cyclic stretch
  • Endothelial cells
  • Mechanotransduction
  • Rho-GEF
  • Solo/ARHGEF40
  • VE-cadherin

ASJC Scopus subject areas

  • Cell Biology

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