Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation
Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation
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DOI：
10.1096/fj.06-5809com
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发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Serhan, Charles N.
中科院分区：
文献类型：
--
作者：
Wada, Koichiro;Arita, Makoto;Serhan, Charles N.
白三烯（LTs）和脂质（LXs）是脂质介质，在调节急性炎症反应中起关键作用。它们在神经干细胞（NSC）功能中的作用令人感兴趣。我们在这里发现LTB4和LXA(4)调节从胚胎脑分离的小鼠NSCs的增殖和分化。LTB4刺激NSCs增殖（3 ~ 100 nM），受体拮抗剂阻断NSCs增殖（IC50 = 2.7 μ M）。相比之下，LXA(4)及其阿司匹林触发的-15-epi-LXA(4)稳定类似物在1 nM处就能减弱NSCs的生长。脂氧合酶（LOX）抑制剂和LTB4受体拮抗剂均引起细胞凋亡和细胞死亡。基因芯片分析显示，LTB4对表皮生长因子（EGF）受体、细胞周期蛋白E、p27、caspase 8等生长相关基因的表达有严格调控；LXA(4)给出相反的基因表达。除了增殖外，LTB4还通过神经突生长和MAP2表达来监测NSCs向神经元的分化。这些结果首次表明LTB4和LXA(4)直接调控NSCs的增殖和分化，提示这些新途径可能有助于干细胞的修复。- Wada， K, Arita， M., Nakajima， A., Katayama， K., Kudo， C., Kamisaki， Y., Serhan， C. N.白三烯B-4和脂素A(4)是神经干细胞增殖和分化的调控信号。
Leukotrienes (LTs) and lipoxins (LXs) are lipid mediators that play a key role in regulating acute inflammatory responses. Their roles in neural stem cell (NSC) functions are of interest. We showed here that LTB4 and LXA(4) regulated proliferation and differentiation of murine NSCs that were isolated from embryo brains. Proliferation of NSCs was stimulated by LTB4 (3 to 100 nM) and blocked by receptor antagonist (IC50 = 2.7 mu M). In contrast, LXA(4), and its aspirin-triggered-15-epi-LXA(4) stable analog attenuated growth of NSCs at as little as 1 nM. Both lipoxygenase (LOX) inhibitors and LTB4 receptor antagonists caused apoptosis and cell death. Gene chip analysis revealed that growth-related gene expressions such as epidermal growth factor (EGF) receptor, cyclin E, p27, and caspase 8 were tightly regulated by LTB4; LXA(4) gave the opposite gene expressions. In addition to proliferation, LTB4 induced differentiation of NSCs into neurons as monitored by neurite outgrowth and MAP2 expression. These results indicate for the first time that LTB4 and LXA(4) directly regulate proliferation and differentiation of NSCs, suggesting these new pathways may be useful in restoring stem cells. - Wada, K., Arita, M., Nakajima, A., Katayama, K., Kudo, C., Kamisaki, Y., Serhan, C. N. Leukotriene B-4 and lipoxin A(4) are regulatory signals for neural stem cell proliferation and differentiation.