PKA/ERK与JAK2/STAT3信号串扰在褪黑激素介导单色光刺激鸡肝脏IGF-1分泌中的作用

Our previous studies found that monochromatic green light stimulated IGF-1 secretion in the liver, and IGF-1 combined with its receptors within muscle tissue to promote the proliferation and differentiation of skeletal muscle satellite cells in broilers. However, how the environmental color light information influence the synthesis and secretion of IGF-1 is not clear. The project will investigate the correlation between IGF-1 secretion and expression of melatonin and its receptors, and discuss whether melatonin plays a mediating role of synthesis and secretion of IGF-1 in broiler liver under monochromatic light, and determine the role of melatonin membrane receptor pathways, membrane-nuclear receptors signaling pathways, and crosstalk between PKA/ERK and JAK2/STAT3 signals in affecting by monochromatic light in broiler liver. The study is on the basis of the classical theory, the liver IGF-1 secretion regulated by the hypothalamus – pituitary growth hormone – IGF-1 axis, to clarify the new pathway and molecular mechanism of liver IGF-1 synthesis and secretion in enviromental color light information via the direct effct of melatonin in boriler. Therefore, the project will be helpful to reveal the internal relationship between the environment factors (such as light spectra) and the avian functional gene expression, and is expected to provide a new theoretical guidance in improving the productive performance in poultry by using new light spectra.

我们的研究发现单色绿光刺激肉鸡肝脏分泌IGF-1，后者与肌肉组织中IGF-1受体结合，促进骨骼肌卫星细胞增殖和分化。但对外界光色信息如何影响鸡肝脏IGF-1的合成与分泌的机制仍不清楚。本项目以前期发现单色光影响褪黑激素分泌为切入点，探究单色光影响鸡肝脏IGF-1分泌与褪黑激素及受体表达的相关性；确定在单色光影响鸡肝脏IGF-1的合成与分泌中，褪黑激素是否发挥介导作用及其作用的膜受体途径、膜-核受体信号通路、胞内信号途径和PKA/ERK与JAK2/STAT3信号的串扰作用等。本研究在经典学说认为肝脏IGF-1分泌受下丘脑-垂体生长激素-IGF-1轴调控的基础上，阐明外界光色信息通过褪黑激素直接作用于鸡肝细胞影响IGF-1的合成与分泌的新路径及其分子作用机制，有助于揭示环境因子（光色）影响机体功能基因表达的内在联系，有望为合理利用光色信息提高家禽生产力提供新的突破点。

光照是影响禽类生产力表现的最主要环境因素之一。我们的前期研究发现单色绿光刺激肉鸡肝脏分泌IGF-1，后者与肌肉组织中IGF-1受体结合，促进骨骼肌卫星细胞增殖和分化，但对外界光色信息如何影响鸡肝脏IGF-1的合成与分泌的机制仍不清楚。本项目设计利用qRT-PCR、Western blot和RNA干扰等生物学技术，结合体内与体外试验研究了褪黑激素介导单色光诱导鸡肝脏IGF-1合成与分泌作用中的受体途径及其胞内信号通路，为进一步利用光色提高家禽生产性能提供理论依据。研究发现：①单色绿光促进肉鸡肝脏发育和IGF-1的合成与分泌。②单色绿光可促进松果体和视网膜表达褪黑激素关键合成酶cAanat和合成褪黑激素，提高血浆褪黑激素水平，并上调肝脏表达褪黑激素膜受体和下调核受体RORα的表达，影响肝脏钟基因表达。③褪黑激素通过特异性结合膜受体（Mel1a和Mel1c）和核受体（RORα）介导了单色光影响鸡肝脏IGF-1的合成过程。④褪黑激素膜受体Mel1a和Mel1c分别激活胞内cAMP/PKA/AKT和Gαq/PKC/ERK信号通路而调节肝脏IGF-1的合成。褪黑激素也可通过Mel1a/cAMP/PKA抑制RORα的表达，导致IκBα的合成降低，对NF-κB的束缚减弱，从而促进NF-κB入核，参与IGF-1的转录调控。这些结果从细胞和分子水平上证明单色光诱导鸡肝细胞增殖和IGF-1分泌的机制：褪黑激素作用假说。研究成果有助于揭示环境因子（光色）影响体内功能基因表达的内在联系规律，有望为合理利用光色信息提高家禽生产力提供新的突破点。