title: Pivotal role of integrin alpha5beta1 in hypotonic stress-induced responses of human endothelium.
abstract: We have previously reported that both hypotonic stress (HTS) and lysophosphatidic acid (LPA) induce ATP release and a transient reorganization of actin through sequential activation of RhoA/Rho-kinase and focal adhesion kinase F-actin (FAK)/paxillin in human umbilical cord vein endothelial cells (HUVECs). LPA is known to induce the activation of RhoA via its specific receptors, but the mechanisms by which HTS initiates these intracellular signals are not known. The present study aimed to identify the molecule(s) that are unique to the sensing and/or transducing the mechanical stress. Reverse transcriptase-polymerase chain reaction revealed the expression of several integrin subunits in HUVECs. Anti-integrin alpha5beta1 antibody (Ab), but not anti-integrin alpha2, alpha6, alpha v, or beta4 antibodies, inhibited HTS-induced RhoA translocation, tyrosine phosphorylation of FAK and paxillin, ATP release, and actin reorganization. However, the LPA-induced ATP release and actin reorganization were not inhibited by any of these anti-integrin antibodies, indicating that integrin alpha5beta1 plays a pivotal role in the HTS-induced but not in the LPA-induced responses. It is therefore reasonable to assume that this particular subtype of integrin is involved in the initiation of the responses induced by mechanical stimuli in HUVECs.
authors.affiliation: Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oike
authors.forename: Michi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Karashima
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology*; D039081:Integrin alpha5beta1 / Q000502:physiology*; D008246:Lysophospholipids / Q000494:pharmacology; D040542:Mechanotransduction, Cellular; D051419:Paxillin / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical; D013312:Stress, Physiological; D014471:Umbilical Veins / Q000166:cytology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D007038:Hypotonic Solutions; D039081:Integrin alpha5beta1; D008246:Lysophospholipids; D051419:Paxillin; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020742:rhoA GTP-Binding Protein; C032881:lysophosphatidic acid