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主动脉瘤中平滑肌细的重编程
作者:小柯机器人 发布时间:2020/4/5 17:47:37

美国耶鲁大学医学院Michael Simons、George Tellides和美国高级人工智能研究实验室Thomas W. Chittenden研究团队合作取得一项新成果。他们揭示了平滑肌细胞重编程促进主动脉瘤进展。相关论文发表在2020年4月2号出版的《细胞-干细胞》杂志上。

在该研究中,研究人员对主动脉瘤发展中不同因素之间的相互作用进行了探究,并确定了平滑肌细胞(SMC)重编程为间充质干细胞(MSC)样细胞起关键作用。在高胆固醇饮食的Apoe-/-小鼠中,SMC转化生长因子β(TGF-β)信号特异性缺失显示出与人类主动脉瘤发展一致的特征,这与将收缩性SMC转分化为MSC样中间物有关,这些中间物可以发育成骨细胞、软骨细胞、脂肪细胞和巨噬细胞。内侧SMC丢失与非SMC主动脉细胞量显著增加相结合导致主动脉旺盛生长和扩张、主动脉壁钙化和骨化以及炎症从而导致动脉瘤的发展。

据悉,人们对主动脉瘤的病因了解甚少,但它与平滑肌中的动脉粥样硬化、高胆固醇血症和异常TGF-β信号有关。

附:英文原文

Title: Smooth Muscle Cell Reprogramming in Aortic Aneurysms

Author: Pei-Yu Chen, Lingfeng Qin, Guangxin Li, Jose Malagon-Lopez, Zheng Wang, Sonia Bergaya, Sharvari Gujja, Alexander W. Caulk, Sae-Il Murtada, Xinbo Zhang, Zhen W. Zhuang, Deepak A. Rao, Guilin Wang, Zuzana Tobiasova, Bo Jiang, Ruth R. Montgomery, Lele Sun, Hongye Sun, Edward A. Fisher, Jeffrey R. Gulcher, Carlos Fernandez-Hernando, Jay D. Humphrey, George Tellides, Thomas W. Chittenden, Michael Simons

Issue&Volume: 2020/04/02

Abstract: The etiology of aortic aneurysms is poorly understood, but it is associated with atherosclerosis,hypercholesterolemia, and abnormal transforming growth factor β (TGF-β) signalingin smooth muscle. Here, we investigated the interactions between these different factorsin aortic aneurysm development and identified a key role for smooth muscle cell (SMC)reprogramming into a mesenchymal stem cell (MSC)-like state. SMC-specific ablationof TGF-β signaling in Apoe/ mice on a hypercholesterolemic diet led to development of aortic aneurysms exhibitingall the features of human disease, which was associated with transdifferentiationof a subset of contractile SMCs into an MSC-like intermediate state that generatedosteoblasts, chondrocytes, adipocytes, and macrophages. This combination of medialSMC loss with marked increases in non-SMC aortic cell mass induced exuberant growthand dilation of the aorta, calcification and ossification of the aortic wall, andinflammation, resulting in aneurysm development.

DOI: 10.1016/j.stem.2020.02.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30066-7

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx