Stem Cells and Diabetes Section, National Center for Cell Science, Ganeshkhind Road, Pune, India.
Islets. 2009 Sep-Oct;1(2):137-47. doi: 10.4161/isl.1.2.9578.
Epithelial-to-mesenchymal transition is a phenomenon necessary for embryonic development and also seen during certain pathological conditions. We show here for the first time that reduction in miR-30 family microRNAs, is responsible for mesenchymal transition of primary cultures of human pancreatic epithelial cells. We found that miR-30 family microRNAs target mesenchymal gene transcripts and maintain them in a translationally inactive state. Forced depletion using miR-30 family specific anti-miRs leads to mesenchymal transition while ectopic overexpression maintains the epithelial phenotype. We also show that miR-30 family microRNAs increase in abundance during differentiation of pancreatic islet-derived mesenchymal cells into hormone-producing islet-like cell aggregates. Our studies in human adult diseased pancreas also demonstrate that miR-30 family microRNAs are expressed at lower abundance in fibrotic lesions during pancreatitis. Together, our data confirm that miR-30 family microRNAs form a part of the regulatory signaling events involved in cellular response of pancreatic epithelial cells during mesenchymal transition.
上皮-间充质转化是胚胎发育所必需的现象，也可见于某些病理状况。我们首次证明，miR-30 家族 microRNAs 的减少导致人胰腺上皮细胞原代培养的间充质转化。我们发现，miR-30 家族 microRNAs 靶向间充质基因转录本，并使它们处于翻译失活状态。使用 miR-30 家族特异性抗 microRNA 的强制耗尽导致间充质转化，而异位过表达则维持上皮表型。我们还表明，miR-30 家族 microRNAs 在胰腺胰岛衍生的间充质细胞分化为产生激素的胰岛样细胞聚集体的过程中丰度增加。我们在人类成年病变胰腺中的研究也表明，miR-30 家族 microRNAs 在胰腺炎期间纤维化病变中的表达丰度较低。总之，我们的数据证实，miR-30 家族 microRNAs 构成参与胰腺上皮细胞在间充质转化过程中的细胞反应的调节信号事件的一部分。
