Transdifferentiation of bone marrow-derived endothelial progenitor cells into the smooth muscle cell lineage mediated by tansforming growth factor-β1
Transdifferentiation of bone marrow-derived endothelial progenitor cells into the smooth muscle cell lineage mediated by tansforming growth factor-β1
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DOI：
10.1016/j.atherosclerosis.2010.02.040
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发表时间：
2010-07-01
期刊：
影响因子：
5.3
通讯作者：
Kikuta, Ken-ichiro
中科院分区：
文献类型：
--
作者：
Imamura, Hirotoshi;Ohta, Tsuyoshi;Kikuta, Ken-ichiro
目的：本研究的目的是在体外和体内研究骨髓（BM）来源的内皮祖细胞（EPC）向平滑肌细胞（SMC）谱系的转分化。方法和结果：从大鼠骨髓中获得EPC并进行培养。布连蛋白包被的培养皿持续 15 天。用转化生长因子（TGF）-β1处理EPCs 7天，改变了EPCs的形态，减少了EPCs内皮标志物的表达，诱导了SMC标志物的表达，并增强了其增殖。 EPC 表达 II 型 TGF-β 受体 (TGF-β RII)，TGF-β 1 诱导 EPC 中 Smad 2 的磷酸化。 TGF-β 1 诱导的转分化可被 TGF-β 中和抗体和 TGF-β RII 基因沉默特异性抑制。自体EPCs的局部移植在第28天增强了球囊损伤动脉的内膜增生。移植的EPCs在第14天定位于内皮层附近，但在第28天广泛分布在肥厚的新内膜内，分化为SMC谱系。 EPCs 移植既不会促进生长因子（例如 TGF-β1）的表达，也不会促进裸露动脉内的早期炎症反应。结论：TGF-β 1 诱导 TGF-β RII 介导的 BM 来源的 EPC 向 SMC 谱系的转分化。通过 EPC 移植增强内膜增生可能是由于 TGF-β 1 诱导的 EPC 转分化和增殖。(C) 2010 Elsevier Ireland Ltd. 保留所有权利。
Objective: The aim of this study was to investigate the transdifferentiation of bone marrow (BM)-derived endothelial progenitor cells (EPCs) into the smooth muscle cell (SMC) lineage in vitro and in vivo.Methods and results: EPCs were obtained from BM of rats and cultured on. bronectin-coated dishes for 15 days. Treatment of EPCs with transforming growth factor (TGF)-beta 1 for 7 days changed morphology of EPCs, reduced the expression of endothelial markers in EPCs, induced the expression of SMC markers, and enhanced their proliferation. EPCs expressed TGF-beta receptor type II (TGF-beta RII) and TGF-beta 1 induced the phosphorylation of Smad 2 in EPCs. TGF-beta 1-induced transdifferentiation was specifically inhibited by neutralizing antibody against TGF-beta and gene silencing of TGF-beta RII. Local transplantation of autologous EPCs enhanced intimal hyperplasia of the balloon-injured artery on day 28. Transplanted EPCs were localized near the endothelial layer on day 14 but widely distributed within the hypertrophic neointima on day 28 differentiating toward SMC lineage. Neither expression of growth factors such as TGF-beta 1 nor early inflammatory reactions within the denuded arteries were promoted by transplantation of EPCs. Conclusions: TGF-beta 1 induced the transdifferentiation of BM-derived EPCs toward SMC lineage mediated by TGF-beta RII. The augmentation of intimal hyperplasia by transplantation of EPCs was probably due to the transdifferentiation and proliferation of EPCs induced by TGF-beta 1. (C) 2010 Elsevier Ireland Ltd. All rights reserved.