Zhang Tianliang, Leng Zhaoting, Liu Wenjing, Wang Xia, Yan Xue, Yu Li
Medicine Research Center, Weifang Medical University, Shandong, PR China.
Department of Histology and Embryology, Weifang Medical University, Shandong, PR China.
Neurosci Lett. 2015 May 6;594:6-11. doi: 10.1016/j.neulet.2015.03.046. Epub 2015 Mar 25.
Neural tube defects (NTDs) are common congenital malformations. Mitogen-activated protein kinases (MAPKs) pathway is involved in many physiological processes. HMGB1 has been showed closely associated with neurulation and NTDs induced by hyperthermia and could activate MAPKs pathway. Since hyperthermia caused increased activation of MAPKs in many systems, the present study aims to investigate whether HMGB1 contributes to hyperthermia induced NTDs through MAPKs pathway. The mRNA levels of MAPKs and HMGB1 between embryonic day 8.5 and 10 (E8.5-10) in hyperthermia induced defective neural tube were detected by real-time quantitative polymerase chain reaction (qPCR). By immunofluorescence and western blotting, the expressions of HMGB1 and phosphorylated MAPKs (ERK1/2, JNK and p38) in neural tubes after hyperthermia were studied. The mRNA levels of MAPKs and HMGB1, as well as the expressions of HMGB1 along with phosphorylated JNK, p38 and ERK, were downregulated in NTDs groups induced by hyperthermia compared with control. The findings suggested that HMGB1 may contribute to hyperthermia induced NTDs formation through decreased cell proliferation due to inhibited phosphorylated ERK1/2 MAPK.
神经管缺陷（NTDs）是常见的先天性畸形。丝裂原活化蛋白激酶（MAPKs）通路参与许多生理过程。已有研究表明，高迁移率族蛋白B1（HMGB1）与神经胚形成以及热诱导的神经管缺陷密切相关，并且能够激活MAPKs通路。由于热在许多系统中导致MAPKs的激活增加，本研究旨在探讨HMGB1是否通过MAPKs通路促成热诱导的神经管缺陷。通过实时定量聚合酶链反应（qPCR）检测热诱导的神经管缺陷胚胎在胚胎第8.5天至10天（E8.5 - 10）期间MAPKs和HMGB1的mRNA水平。通过免疫荧光和蛋白质印迹法，研究热作用后神经管中HMGB1和磷酸化MAPKs（ERK1/2、JNK和p38）的表达。与对照组相比，热诱导的神经管缺陷组中MAPKs和HMGB1的mRNA水平以及HMGB1与磷酸化JNK、p38和ERK的表达均下调。研究结果表明，HMGB1可能通过抑制磷酸化ERK1/2 MAPK导致细胞增殖减少，从而促成热诱导的神经管缺陷形成。
