Kwon Yong-Jun, Sun Yuanjie, Kim Nam-Ho, Huh Sung-Oh
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, Gangwon-do 200-702, South Korea.
Biochem Biophys Res Commun. 2009 Mar 13;380(3):655-9. doi: 10.1016/j.bbrc.2009.01.159. Epub 2009 Jan 29.
Lysophospholipids regulate a wide array of biological processes including cell survival and proliferation. In our previous studies, we found that in addition to SRE, CRE is required for maximal c-fos promoter activation triggered by lysophosphatidic acid (LPA). c-fos is an early indicator of various cells into the cell cycle after mitogenic stimulation. However, role of CREB activation in LPA-stimulated proliferation has not been elucidated yet. Here, we investigate how LPA induces proliferation in Rat-2 fibroblast cell via CREB activation. We found that total cell number and BrdU-positive cells were increased by LPA. Moreover, levels of c-fos mRNA and cyclin D1 protein were increased via LPA-induced CREB phosphorylation. Furthermore, LPA-induced Rat-2 cell proliferation was decreased markedly by ERK inhibitor (U0126) and partially by MSK inhibitor (H89). Taken together, these results suggest that CREB activation could partially up-regulate accumulation of cyclin D1 protein level and proliferation of LPA-stimulated Rat-2 fibroblast cells.
溶血磷脂调节包括细胞存活和增殖在内的一系列生物学过程。在我们之前的研究中，我们发现除了SRE外，溶血磷脂酸（LPA）触发的最大c-fos启动子激活还需要CRE。c-fos是有丝分裂原刺激后各种细胞进入细胞周期的早期指标。然而，CREB激活在LPA刺激的增殖中的作用尚未阐明。在这里，我们研究LPA如何通过CREB激活诱导大鼠-2成纤维细胞增殖。我们发现LPA增加了总细胞数和BrdU阳性细胞。此外，c-fos mRNA和细胞周期蛋白D1蛋白水平通过LPA诱导的CREB磷酸化而增加。此外，ERK抑制剂（U0126）显著降低了LPA诱导的大鼠-2细胞增殖，MSK抑制剂（H89）部分降低了该增殖。综上所述，这些结果表明CREB激活可能部分上调细胞周期蛋白D1蛋白水平的积累以及LPA刺激的大鼠-2成纤维细胞的增殖。
