Abstract:
The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.
感知温度变化的能力对哺乳动物的生存至关重要。哺乳动物主要是通过温度敏感型瞬时受体电位通道(Thermosensitive transient receptor potential channels, Thermo-TRPs)感应温度变化。一些哺乳类动物为了度过寒冷的冬季并存活下来会进入冬眠状态,在此期间它们的体温有剧烈波动;然而,这些哺乳动物具有哪些潜在的温度感受(thermal response)调节机制还不清楚。我们运用实时荧光聚合酶链式反应和蛋白质免疫印记等方法,发现大足鼠耳蝠( Myotis ricketti) 在冬季蛰伏期会高表达热激活通道TRPs(例如TRPV1和TRPV4),而在夏季活跃期则高表达冷激活TRPs(例如,TRPM8和TRPC5)。我们也发现小鼠在温度相对较高的条件(40 oC)下,会高表达冷激活TRPs(例如 Trpm8 和 Trpc5 )。这些结果提示,小型哺乳动物在温暖或较热的状况下,会上调表达冷激活TRPs。通过结合位点分析,我们发现一些同源异型盒(HOX)转录因子(Transcription factor, TF)可以调节热激活和冷激活TRPs基因的表达,而POU(Pit-Oct-Unc)家族的一些转录因子则调节温热敏感和冷激活TRPs基因的表达。双荧光素酶报告基因检测结果表明,转录因子HOXA9,POU3F1和POU5F1调节 TRPC5 的表达,可见Thermo-TRPs基因是受到HOX和POU家族中多个转录因子在不同水平上的调控。这项研究揭示蝙蝠为了在冬眠中存活下来,而采取的温度感觉适应机制。.