Adiponectin and adiponectin receptor genes are coexpressed during zebrafish embryogenesis and regulated by food deprivation.

Adiponectin is an adipocytokine that plays important roles in glucose and lipid homeostasis. Adiponectin binds to two types of transmembrane receptors: Adiponectin receptor (AdipoR) type 1 and 2. We isolated and characterized the two adiponectin genes (adiponectin A and B) and the three adiponectin receptors in zebrafish. In adult, adiponectin A is only detected in the kidney while adiponectin B mRNAs are widely expressed and are detected in the liver, adipose tissue, muscle, and brain. The receptors are found in many tissues such as the brain, gut, liver, adipose tissue, kidney, and ovary. Interestingly, we detect embryonic synexpression of all genes in the pharyngeal region. We observed that adiponectin B expression in adult liver is reduced while the expression of the receptors is increased in fasted fish. These data indicate that the upstream members of the Adiponectin pathway have complex expression patterns and are regulated by food deprivation in zebrafish.     

幼年特发性关节炎的致病基因与通路分析

目的 探索幼年特发性关节炎(JIA)的发病机理,并找到可能在JIA中起重要作用的分子靶标.方法 通过分析美国国家生物信息技术中心(NCBI)的公共基因芯片数据库(GEO)中关于JIA研究的表达谱芯片数据,找到JIA的差异表达基因,并通过GLAD4U和ToppGene数据库对差异表达基因进行优化和补充,找到JIA的致病基因,利用DAVID在线工具对致病基因进行功能富集分析,探索JIA发病和发展过程中发生的主要生物过程及其重要的基因.结果 得到了JIA的致病基因列表及这些基因所富集的功能,找到了可能在JIA中发挥重要作用的生化通路,如细胞因子与细胞因子受体相互作用(Cytokine-cytokine receptor interaction) 、Jak-STAT信号通路(Jak-STAT signaling pathway)等.结论 通过生物信息学分析的方法了解JIA的发病机理,找到可能致病的候选基因,为实验研究和临床治疗节约时间和成本.     

NZB/W狼疮鼠体外IFN-α信号调控网络研究

通过IFN-α刺激基因(ISG)表达谱勾画SLE发病机制中可能的IFN-α异常调控通路。采用基因芯片技术,比较分析发病前新西兰黑/白(NZB/W)F1代狼疮鼠和年龄性别相匹配的对照组BALB/c小鼠脾脏单个核细胞3 h干扰素刺激基因表达谱,并运用信号通路分析软件(CRSD)解析IFN-α信号调控网络。结果:IFN-α体外刺激诱导上调了BALB/c小鼠而非NZB/W狼疮鼠脾脏单个核细胞p53通路相关基因转录产物的表达;IFN-α共同诱导了NZB/W狼疮鼠和BALB/c小鼠Th1型细胞因子和趋化因子网络,相对于BALB/c鼠,IFN-α刺激后IL15、IP10、XCL1、CCL3、CCL7及CCL12的转录产物在NZB/W狼疮鼠中高表达(P值均<0.01)。NZB/W狼疮鼠对IFN-α抑制细胞增殖作用和促炎作用的异常反应,参与并加重了NZB/W狼疮鼠自身免疫性疾病的进展。     

小鼠蛛网膜下腔出血后海马CA1区mGluR1和ERK1/2的表达变化

目的:探讨小鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后代谢型谷氨酸受体1(metabotropicglutamate receptor 1,mGluR1)及细胞外信号调节激酶1/2(ERK1/2)调控神经细胞凋亡的分子机制。方法:采用非开颅血管内穿线法制备小鼠SAH模型,随机分为3组:假手术组、SAH+生理盐水(SAH+NS)组、SAH+LY367385(mGluR1抑制剂,SAH+LY367385)组,于SAH后10 min侧脑室注射生理盐水或LY367385(500 nmol/L)5μl,术后行神经功能评分。分别在SAH后6、24、48 h 3个时间点取右侧脑组织标本,逆转录-聚合酶链式反应(RT-PCR)检测各组mGluR1的表达变化,免疫印迹法(Western Blot)检测p-ERK1/2蛋白的表达,TUNEL法检测右侧海马CA1区神经细胞的凋亡。结果:与假手术组比较,SAH+NS组小鼠神经功能评分均显著降低(P<0.05),随SAH时间延长,各组小鼠mGluR1、p-ERK1/2蛋白均有不同程度增强,凋亡细胞增多(P<0.05)。与SAH+NS组比较,SAH+LY367385组小鼠神经功能评分增加,mGluR1、p-ERK1/2蛋白表达均有不同程度下调,神经细胞凋亡数目有所减少。SAH后6～48 h,mGluR1的表达与p-ERK1/2呈正相关。结论:mGluR1和ERK在SAH的发病机制中发挥了重要作用,SAH后海马内mGluR1的表达增强可通过激活ERK信号途径诱导神经细胞的凋亡。     

Isolation and expression analysis of three zebrafish angiopoietin genes.

The Tie1 and Tie2 receptor tyrosine kinases and the Tie2 ligands, the angiopoietins, play critical roles in vertebrate vascular embryogenesis, helping to mediate the interaction between endothelial cells and the pericytes or vascular smooth muscle cells that envelop and support them. We have obtained full-length cDNA sequences for zebrafish orthologs of angiopoietin-1 (ang1), angiopoietin-2 (ang2), and angiopoietin-like-3 (angptl3). Ang1 is expressed in head ventral mesenchyme, in the ventromedial region of somites, in mesenchyme surrounding trunk axial vessels, and in the hypochord, a transient embryonic structure of endodermal origin that has been implicated in dorsal aorta assembly in both zebrafish and Xenopus. Ang2 is expressed in head and anterior trunk ventral mesenchyme and the developing pronephric glomeruli. Angptl3 is expressed in the yolk syncytial layer.