MicroRNA-155 Promotes the Directional Migration of Resident Smooth Muscle Progenitor Cells by Regulating Monocyte Chemoattractant Protein 1 in Transplant Arteriosclerosis
MicroRNA-155 Promotes the Directional Migration of Resident Smooth Muscle Progenitor Cells by Regulating Monocyte Chemoattractant Protein 1 in Transplant Arteriosclerosis
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MicroRNA-155 通过调节移植动脉硬化中的单核细胞趋化蛋白 1 促进常驻平滑肌祖细胞的定向迁移
DOI：
10.1161/atvbaha.115.306691
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发表时间：
2016-06-01
影响因子：
8.7
通讯作者：
Xia, Jiahong
中科院分区：
文献类型：
--
作者：
Sun, Yuan;Wang, Ke;Xia, Jiahong
平滑肌样细胞是移植动脉硬化病变的主要细胞成分。本研究探讨了平滑肌样细胞的起源、其在新生内膜中积累的机制以及驱动这些过程的因素。方法和结果-通过将miR-155（-/-）骨髓细胞移植到miR-155（+/+）小鼠中建立小鼠主动脉移植模型。发现microRNA-155在移植物动脉硬化中发挥功能性作用。此外，我们发现，非骨髓来源的前体细胞与早期分化的平滑肌和干细胞的标记在移植外膜平滑肌前体细胞。纯化的平滑肌祖细胞在体外经血小板衍生生长因子-BB诱导表达成熟的平滑肌细胞标志物。在体内，这些细胞可以从外膜迁移到内膜，并可能促进新生内膜增生。骨髓来源的细胞中microRNA-155的缺失降低了同种异体移植物内膜和外膜之间单核细胞趋化蛋白1的浓度梯度，这减少了平滑肌祖细胞从外膜向新生内膜的迁移。结论-这项研究表明，microRNA-155通过调节单核细胞趋化蛋白1浓度梯度，促进平滑肌祖细胞从外膜定向迁移，加重移植动脉硬化。
Objective-Smooth muscle-like cells are major cell components of transplant arteriosclerosis lesions. This study investigated the origin of the smooth muscle-like cells, the mechanisms responsible for their accumulation in the neointima, and the factors that drive these processes.Approach and Results-A murine aortic transplantation model was established by transplanting miR-155(-/-) bone marrow cells into miR-155(+/+) mice. MicroRNA-155 was found to play a functional role in the transplant arteriosclerosis. Moreover, we found that the nonbone marrow-derived progenitor cells with markers of both early differentiated smooth muscles and stem cells in the allograft adventitia were smooth muscle progenitor cells. Purified smooth muscle progenitor cells expressed a mature smooth muscle cell marker when induced by platelet-derived growth factor-BB in vitro. In vivo, these cells could migrate into the intima from the adventitia and could contribute to the neointimal hyperplasia. The loss of microRNA-155 in bone marrow-derived cells decreased the concentration gradient of monocyte chemoattractant protein 1 between the intima and the adventitia of the allografts, which reduced the migration of smooth muscle progenitor cells from the adventitia into the neointima.Conclusions-This study demonstrated that microRNA-155 promoted the directional migration of smooth muscle progenitor cells from the adventitia by regulating the monocyte chemoattractant protein 1 concentration gradient, which aggravated transplant arteriosclerosis.