Inhibition of Ca2+/calmodulin-dependent protein kinase or epidermal growth factor receptor tyrosine kinase abolishes lysophosphatidic acid-mediated DNA-synthesis in human myometrial smooth muscle cells

Cell Biology International
Ulrika K Nilsson, Samuel P S Svensson

Abstract

Human myometrial smooth muscle cells (SMCs) were used to evaluate the proliferative activity of lysophosphatidic acid (LPA). This study specifically focuses on the role of Ca(2+)/calmodulin-dependent protein (CaM) kinase and epidermal growth factor (EGF) receptor tyrosine kinase. Myometrial SMCs were cultured from biopsies taken at Cesarean sections. The expression of LPA receptors was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and DNA-synthesis was measured by [3H]thymidine incorporation. LPA(1), LPA(2), and LPA(3)receptor subtypes were detected in the SMCs using RT-PCR. KN-62, an inhibitor of CaM kinase, and Tyrphostin AG 1478, an inhibitor of EGF receptor tyrosine kinase, dose-dependently decreased LPA-stimulated [3H]thymidine incorporation. Furthermore, BB-3103, an inhibitor of matrix metalloproteinases (MMPs), also reduced DNA-synthesis induced by LPA in these cells. The results show, for the first time, that human myometrial SMCs express all three known LPA receptor subtypes. Growth stimulatory effects of LPA on myometrial SMCs seems to be mediated by several pathways, where transactivation of EGF receptors through MMPs appears to be of importance. Furthermore, CaM kinase activity may be criti...Continue Reading

Citations

Oct 20, 2009·Trends in Endocrinology and Metabolism : TEM·Xiaoqin Ye, Jerold Chun
Mar 16, 2007·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·M T Walsh, R Costello
Dec 3, 2009·The FEBS Journal·Pablo Sánchez-GonzálezAntonio Villalobo
Feb 18, 2017·International Journal of Molecular Sciences·Beatrice Mihaela RaduSanda Maria Cretoiu
Aug 21, 2004·Blood·Savita BaggaJoshua A Boyce

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