Suppressed expression of mitogen-activated protein kinases in hyperthermia induced defective neural tube.

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.