Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells

Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells
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DOI:
10.1006/excr.2002.5561
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发表时间:
2002-08-01
影响因子:
3.7
通讯作者:
Spector, M
Spector, M
中科院分区:
医学3区
文献类型:
--
作者:
Kinner, B;Zaleskas, JM;Spector, M

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先前的研究已经证明,在骨髓基质细胞中表达一种收缩肌动蛋白亚型--α-平滑肌肌动蛋白。目前研究的一个目标是将人骨髓基质来源的间充质干细胞的收缩能力与α-平滑肌肌动蛋白的表达联系起来。第二个目标是确定转化生长因子-β1、血小板衍生生长因子-BB和微丝修饰剂对α-平滑肌肌动蛋白表达和α-平滑肌肌动蛋白激活收缩的影响。成人骨髓基质细胞在单层传代,并证明了其向软骨细胞、成骨细胞和成脂表型的诱导能力。采用免疫印迹分析和密度计量法对细胞的α-平滑肌肌动蛋白含量进行定量,并通过种植细胞的I型胶原-糖胺聚糖海绵样基质的收缩来评价细胞的收缩能力。转化生长因子-β1(I ng/ml)显著增加,而血小板衍生生长因子-BB(10 ng/ml)则降低α-平滑肌肌动蛋白的表达和细胞的收缩能力。细胞松弛素D也能抑制细胞收缩。经线性回归分析,细胞介导的收缩与基质DNA含量和细胞α-平滑肌肌动蛋白含量呈显著正相关(R2=0.88)。这些发现为研究α-平滑肌肌动蛋白激活的收缩在间充质干细胞及其结缔组织细胞后代中的作用奠定了基础。(C)2002年埃尔塞维尔科学公司(美国)。
Prior studies have demonstrated the expression of a contractile actin isoform, a-smooth muscle actin, in bone marrow stromal cells. One objective of the current study was to correlate contractility with a-smooth muscle actin expression in human bone marrow stroma-derived mesenchymal stem cells. A second objective was to determine the effects of transforming growth factor-beta1, platelet derived growth factor-BB, and a microfilament-modifying agent on a-smooth muscle actin expression and a-smooth muscle actin-enabled contraction. Adult human bone marrow stromal cells were passaged in monolayer and their inducibility to chondrocytic, osteoblastic, and adipogenic phenotypes was demonstrated. Western blot analysis was employed along with densitometry to quantify the a-smooth muscle actin content of the cells and their contractility was evaluated by their contraction of a type I collagen-glycosaminoglycan sponge-like matrix into which they were seeded. Transforming growth factor-pi (I ng/ml) significantly increased and platelet-derived growth factor-BB (10 ng/ml) decreased a-smooth muscle actin expression and the contractility of the cells. Cytochalasin D also blocked cell contraction. There was a notably high correlation of cell-mediated contraction normalized to the DNA content of the matrices with a-smooth muscle actin content of the cells by linear regression analysis (R-2 = 0.88). These findings lay the groundwork for considering the role of a-smooth muscle actin-enabled contraction in mesenchymal stem cells and in their connective tissue cell progeny. (C) 2002 Elsevier Science (USA).