title: Rho guanine nucleotide exchange factors involved in cyclic-stretch-induced reorientation of vascular endothelial cells.
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 cyclic-stretch-induced endothelial cell reorientation.
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors: Hiyori
authors: H
authors: Abiko
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors: Sachiko
authors: S
authors: Fujiwara
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan kohashi@biology.tohoku.ac.jp kmizuno@biology.tohoku.ac.jp.
authors: Kazumasa
authors: K
authors: Ohashi
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors: Ryuichi
authors: R
authors: Hiatari
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors: Toshiya
authors: T
authors: Mashiko
authors: Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi 980-8579, Japan.
authors: Naoya
authors: N
authors: Sakamoto
authors: Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi 980-8579, Japan.
authors: Masaaki
authors: M
authors: Sato
authors: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan kohashi@biology.tohoku.ac.jp kmizuno@biology.tohoku.ac.jp.
authors: Kensaku
authors: K
authors: Mizuno
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D034741:RNA, Small Interfering / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000187:drug effects; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D004533:Egtazic Acid; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D020742:rhoA GTP-Binding Protein; D000099152:Cadherin 5; C577222:ARHGEF12 protein, human; C505620:ARHGEF40 protein, human
keywords: Cyclic stretch; Endothelial cells; Mechanotransduction; Rho‐GEF; Solo/ARHGEF40; VE‐cadherin