热休克蛋白70抑制剂通过p44/p42丝裂原活化蛋白激酶抑制胰岛素样生长因子-I刺激的成骨细胞迁移。
HSP70 Inhibitor Suppresses IGF-I-Stimulated Migration of Osteoblasts through p44/p42 MAP Kinase.
作者信息
Kawabata Tetsu, Tokuda Haruhiko, Sakai Go, Fujita Kazuhiko, Matsushima-Nishiwaki Rie, Kuroyanagi Gen, Otsuka Takanobu, Kozawa Osamu
机构信息
Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
出版信息
Biomedicines. 2018 Nov 21;6(4):109. doi: 10.3390/biomedicines6040109.
Heat shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone in a variety of cells including osteoblasts. We previously showed that insulin-like growth factor-I (IGF-I) elicits migration of osteoblast-like MC3T3-E1 cells through the activation of phosphatidylinositol 3-kinase/Akt and p44/p42 mitogen-activated protein (MAP) kinase. In the present study, we investigated the effects of HSP70 inhibitors on the IGF-I-elicited migration of these cells and the mechanism involved. The IGF-I-stimulated osteoblast migration evaluated by a wound-healing assay and by a transwell cell migration was significantly reduced by VER-155008 and YM-08, which are both HSP70 inhibitors. VER-155008 markedly suppressed the IGF-I-induced phosphorylation of p44/p42 MAP kinase without affecting that of Akt. In conclusion, our results strongly suggest that the HSP70 inhibitor reduces the IGF-I-elicited migration of osteoblasts via the p44/p42 MAP kinase.
热休克蛋白70（HSP70）是一种在包括成骨细胞在内的多种细胞中普遍表达的分子伴侣。我们之前表明，胰岛素样生长因子-I（IGF-I）通过激活磷脂酰肌醇3激酶/Akt和p44/p42丝裂原活化蛋白（MAP）激酶，引发成骨样MC3T3-E1细胞的迁移。在本研究中，我们研究了HSP70抑制剂对IGF-I引发的这些细胞迁移的影响及其相关机制。通过伤口愈合试验和Transwell细胞迁移评估的IGF-I刺激的成骨细胞迁移，被两种HSP70抑制剂VER-155008和YM-08显著降低。VER-155008显著抑制IGF-I诱导的p44/p42 MAP激酶磷酸化，而不影响Akt的磷酸化。总之，我们的结果强烈表明，HSP70抑制剂通过p44/p42 MAP激酶减少IGF-I引发的成骨细胞迁移。
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