Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Diabetes. 2013 Mar;62(3):887-95. doi: 10.2337/db12-0451. Epub 2012 Dec 6.
Elucidating the mechanism underlying the poor proliferative capacity of adult pancreatic β-cells is critical to regenerative therapeutic approaches for diabetes. Here, we show that the microRNA (miR)-7/7ab family member miR-7a is enriched in mouse adult pancreatic islets compared with miR-7b. Remarkably, miR-7a targets five components of the mTOR signaling pathway. Further, inhibition of miR-7a activates mTOR signaling and promotes adult β-cell replication in mouse primary islets, which can be reversed by the treatment with a well-known mTOR inhibitor, rapamycin. These data suggest that miR-7 acts as a brake on adult β-cell proliferation. Most importantly, this miR-7-mTOR proliferation axis is conserved in primary human β-cells, implicating miR-7 as a therapeutic target for diabetes.
阐明成年胰腺β细胞增殖能力差的机制对于糖尿病的再生治疗方法至关重要。在这里，我们表明，与 miR-7b 相比，microRNA (miR)-7/7ab 家族成员 miR-7a 在小鼠成年胰岛中富集。值得注意的是，miR-7a 靶向 mTOR 信号通路的五个组成部分。此外，抑制 miR-7a 可激活 mTOR 信号通路并促进小鼠原代胰岛中成年β细胞的复制，用众所周知的 mTOR 抑制剂雷帕霉素处理可逆转这种作用。这些数据表明，miR-7 作为成年β细胞增殖的制动器。最重要的是，该 miR-7-mTOR 增殖轴在原代人β细胞中保守，提示 miR-7 可作为糖尿病的治疗靶点。
