Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1
Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1
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DOI：
10.1016/j.bbrc.2015.05.097
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发表时间：
2015-08-14
影响因子：
3.1
通讯作者：
Bae, Sun Sik
中科院分区：
文献类型：
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作者：
Ha, Jung Min;Yun, Sung Ji;Bae, Sun Sik
哺乳动物雷帕霉素靶蛋白复合物（mTORC）调节多种细胞过程，包括增殖、生长、迁移和分化。在这项研究中，我们发现mTORC1调节血小板衍生生长因子（PDGF）诱导的血管平滑肌细胞（VSMCs）的表型转化。用PDGF刺激收缩性VSMCs显著降低了收缩标志物蛋白的表达，并呈时间和剂量依赖性。此外，血管紧张素II（AngII）诱导的VSMCs收缩被PDGF刺激VSMCs完全阻断。PDGF依赖的VSMC标志基因表达的抑制被磷脂酰肌醇3-激酶（PI3K）、细胞外信号调节激酶（ERK）和mTOR的抑制显著阻断，而p38 MAPK的抑制没有影响。特别是，通过雷帕霉素或Raptor沉默抑制mTORC1显著阻断了VSMC的PDGF依赖性表型变化，而Rictor沉默则没有影响。此外，通过Raptor的沉默，PDGF导致的AngII依赖性收缩的损失显著保留。通过雷帕霉素或Raptor沉默抑制mTORC1显著阻断PDGF诱导的VSMC增殖。综上所述，我们认为mTORC 1在VSMC的PDGF依赖性表型变化中起着重要作用。(C)2015 Elsevier Inc. All rights reserved.
Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. (C) 2015 Elsevier Inc. All rights reserved.