沉默长链非编码RNA Meg3损伤小鼠胰岛细胞的胰岛素分泌功能  

Silencing Long Non-coding RNA Meg3 Impairs the Ability of Insulin Secretion in Mice

作　　者：胡艳妹[1] 尤梁惠[2] 朱亚男[2] 德伟[2] 王敏[1] 

机构地区：[1]铜陵职业技术学院医学系,安徽铜陵244000 [2]南京医科大学基础医学院,南京210029

出　　处：《中国生物化学与分子生物学报》2016年第3期289-294,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：安徽省高校自然科学研究基金重点项目(No.KJ2015A374)资助~~

摘　　要：MEG3是一种长链非编码RNA。已有研究证明,鼠源Meg3参与小鼠诱导多能干细胞、神经元和视网膜的分化过程。最新报道,MEG3在人胰岛β细胞中高表达,但其对维持成年胰岛β细胞的功能尚不清楚。本研究旨在探讨Meg3在小鼠胰岛细胞胰岛素分泌功能中的作用。实时定量PCR揭示,与Balb/c小鼠心、肝、脾、肺、肌、肾等组织/器官比较,Meg3在胰腺组织中高表达。在非糖尿病小鼠发生自发性糖尿病的第8、12周,Meg3在胰岛中的表达水平分别下调24%±8%和29%±9%(P<0.01);而当血糖升高20 mmol/L,小鼠胰岛中Meg3表达下调72%±16%(P<0.01)。在MIN6细胞中采用RNA干扰敲减Meg3的表达,在高糖浓度(20 mmol/L)刺激条件下,胰岛素分泌显著减少。小鼠静脉注射si RNA,结合血糖测定或葡萄糖耐受试验(IPGTT)显示,si-Meg3小鼠血清胰岛素水平显著下降。注射葡萄糖前血糖升高,注射葡萄糖后耐受能力降低;免疫组化分析显示,si-Meg3小鼠胰岛素阳性细胞的面积减少。实验结果提示,Meg3通过参与胰岛素的合成和分泌维持成年小鼠胰岛功能。Meg3表达失调可能参与I型糖尿病(T1DM)发病过程。MEG3,a long chain non-coding RNA has been shown to be involved in the differentiation of the induced pluripotent stem（ i PS） cells,neurons and retina in mice. The latest report has found that the human MEG3 is highly expressed in islet beta cells. However,less is known about its role in the maintenance of adult islet beta cells. This study aims to unravel the role of Meg3 in the insulin secretion of mouse beta cells. Real time-quantitative PCR（ RT-q PCR） revealed that Meg3 was highly expressed in the pancreatic tissue,compared with the heart,liver,spleen,lung,muscle,kidney tissues/organs in Balb/c mice. In 8 th and 12 th week of induction of the spontaneous diabetes disease in mice,the expression of Meg3 in the islet was significantly down-regulated by 24% ± 8% and 29% ± 9%,respectively（ P〈0. 01）,particularly the level of Meg3 expression in the islet was declined by 72% ±16% when the level of blood glucose was 20 mmol/L. Silencing Meg3 expression in MIN6 cells by RNAinterference（ RNAi） led to a great decrease in the secretion of insulin under high glucose concentration（ 20 mmol/L） stress. Blood glucose test and glucose tolerance test（ IPGTT） showed that intravenous injection of small interference RNA（ si RNA） resulted in marked decreases of serum insulin levels and glucose tolerance in mice. Immunohistochemical analysis showed that the area of the tissue containing insulin-positive cells in si-Meg3 mice was reduced. Our findings indicate that Meg3 can maintain islet function by participating in the synthesis and secretion of insulin in adult mice. Our findings also suggested that the deregulation of Meg3 may be involved in the development of type 1 diabetes.

关 键 词：lncRNA Meg3 胰岛素合成和分泌 Β细胞凋亡 

分 类 号：R587.1[医药卫生—内分泌]