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Pivotal role of integrin 5ß1 in hypotonic stress-induced responses of human endothelium

Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

¹Correspondence: Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. E-mail: moike{at}pharmaco.med.kyushu-u.ac.jp

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 5ß1 antibody (Ab), but not anti-integrin 2, 6, v, or ß4 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 5ß1 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.—Hirakawa, M., Oike, M., Watanabe, M., Karashima, Y., Ito, Y. Pivotal role of integrin 5ß1 in hypotonic stress-induced responses of human endothelium.

Key Words: ATP release • tyrosine kinase • RhoA • actin cytoskeleton