Osteoprotegerin induces cytoskeletal reorganization and activates FAK, Src, and ERK signaling in endothelial cells
Osteoprotegerin induces cytoskeletal reorganization and activates FAK, Src, and ERK signaling in endothelial cells
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DOI：
10.1111/j.1600-0609.2010.01446.x
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发表时间：
2010-07-01
影响因子：
3.1
通讯作者：
Holen, Ingunn
中科院分区：
文献类型：
--
作者：
Kobayashi-Sakamoto, Michiyo;Isogai, Emiko;Holen, Ingunn
骨保护素（OPG）是一种可溶性肿瘤坏死因子受体家族成员，由骨和血管系统中的一系列细胞类型表达。然而，OPG在血管系统中的具体作用尚不清楚。我们最近报道，OPG治疗保护内皮细胞免受牙龈卟啉单胞菌（Porphyromonas gingivalis）（成人牙周炎的重要病原体）的半胱氨酸蛋白酶诱导的脱落和凋亡性细胞死亡。我们还发现OPG激活细胞外信号调节激酶（ERK）1/2，这与细胞存活和血管生成有关。在这项研究中，我们表明，暴露于OPG诱导人真皮微血管内皮细胞的形态学变化。我们的研究结果表明，OPG诱导的微管长度的剂量依赖性增加，这与细胞从多边形到细长形状的过渡相一致。此外，我们证明OPG激活信号通路，从而导致Src、粘着斑激酶和ERK 1/2的激活。这些发现表明，OPG调节至少两个不同的途径：一个是通过ERK信号传导诱导细胞增殖，另一个是通过Src信号传导诱导血管生成。本研究的结果表明，OPG可能作为血管生成的调节剂。
Osteoprotegerin (OPG) is a soluble tumor necrosis factor receptor family member that is expressed by a range of cell types in bone as well as in the vasculature. However, the specific role of OPG in the vascular system is unclear. We recently reported that OPG treatment protects endothelial cells from detachment and apoptotic cell death induced by cysteine proteases of Porphyromonas gingivalis, an important pathogen of adult periodontitis. We also found that OPG activates the extracellular signal-regulated kinase (ERK) 1/2, which has been linked to cell survival and angiogenesis. In this study, we demonstrate that exposure to OPG induces a substantial morphological change in human dermal microvascular endothelial cells. Our results show that OPG induced a dose-dependent increase in the length of microtubules, which coincided with the transition of the cells from a polygonal to an elongated shape. Furthermore, we demonstrated that OPG activates signaling pathways that lead to the activation of Src, focal adhesion kinase, and ERK1/2. These findings suggest that OPG regulates at least two distinct pathways: one that induces cell proliferation via ERK signaling and another that induces angiogenesis via Src signaling. The findings of this study suggest that OPG may function as a regulator of angiogenesis.