miR1934,一种脂联素特异性调控的靶microRNA,在肥胖小鼠的脂肪组织中表达降低

mi R1934,an adiponectin specially-regulated microRNA,is downregulated in adipose tissues of obese mice

目的:脂联素(Adiponectin,Ap N)是脂肪细胞分泌的最主要抗炎细胞因子。利用Ap N过表达(Ap N-Over)和Ap N基因敲除(Ap N-KO)小鼠模型筛选出Ap N的靶micro RNAs(mi RNAs),以探寻脂肪组织新的具抗炎作用的功能性mi RNAs。方法:给予4周龄雄性Ap N-Over小鼠和其野生型对照小鼠高脂饮食6周后,分离提取腹股沟脂肪组织。采用mi RNA微陈列芯片筛选出两组小鼠脂肪组织间表达有差异的mi RNAs;在Ap N-Over,Ap N-KO和高脂(HFD)诱发的肥胖小鼠脂肪组织中用定量PCR验证上述筛选出的差异mi RNAs;采用生物信息学数据库预测mi RNAs的靶基因。结果:Ap N-Over小鼠脂肪组织中有12个mi RNAs的表达与野生对照小鼠显著不同;定量PCR验证结果显示有3个mi RNAs确实受到Ap N的调节:mi R532-5p的表达被Ap N下调,而mi R883b-5p和mi R1934的表达被上调;其中仅有mi R1934在Ap N-KO小鼠的脂肪组织中明显下降,与Ap NOver小鼠脂肪组织呈现相反的表达模式;mi R1934在HFD诱发的肥胖小鼠的内脏脂肪组织中的表达明显低于普通饮食喂养的小鼠(1.00±0.22 vs.0.54±0.13,P=0.04)。生物信息数据库预测出mi R1934有53个靶基因,其中2个靶基因为丝氨酸/苏氨酸激酶3(serine/threonine kinase 3,STK3)和趋化因子(C-C motif)配体[chemokine(C-C motif)ligand,CCL19],二者均为参与JNK信号通路的分子。结论:mi R1934是体内脂肪组织中受脂联素特异性调节的mi RNA。肥胖小鼠内脏脂肪组织中mi R1934的表达显著降低;生物信息学分析初步发现mi R1934可能参与调节JNK信号通路。因此脂联素特异性的靶mi R1934有可能为改善脂肪组织炎症及其相关的代谢异常提供新的治疗前景。

Objective：Mice over-expressing Ap N specifically in adipose tissues（AT,Ap N-Over） and the mice knocking-out Ap N（Ap N-KO）were used to identify micro RNAs（mi RNAs）targeted by Ap N in AT. Methods：Male Ap N-Over mice,Ap N-KO mice and C57/Bl6 J mice fed with high-fat diet（HFD）were used. mi RNA expression profiling was performed by using micro RNA arrays. The expressions of mi RNAs and adipokines were quantified by real-time PCR. The gene targets of mi R1934 were predicted by bioinformatic data base. Results：There were 12 mi RNAs differently expressed between AT of Ap N-Overex mice and wild-type mice. By PCR validation,the expression of mi R532-5p was down-regulated,while that of mi R883b-5p and mi R1934 was up-regulated in AT of Ap N-Over mice. Moreover,the expression of mi R1934 in AT of Ap N-KO mice was down-regulated,exhibiting a reverse expression pattern compared to Ap N-Over mice. The expression of mi R1934 was significantly lower in epididymal AT of HFD-induced obese mice than that in chow diet-fed mice（1.00±0.22 vs. 0.54±0.13,P=0.04）. The predicted gene targets of mi R-1934,serine/threonine kinase 3（STK3）and chemokine（C-C motif）ligand（CCL19）,were annotated to be involved in Jun N-terminal kinases（JNK）signaling pathway. Conclusion：We identified a novel mi RNA,mi R-1934,which was up-regulated by Ap N in AT in vivo. The expression of mi R1934 was decreased in visceral AT of obese mice. The possible roles of mi R-1934 may be involved in the JNK signaling pathway.This novel mi RNA may open new therapeutic perspectives for controlling the pro-inflammatory state of obese AT.