B-RAGE – Mediated Augmentation of Angiotensin II – Induced Activation of JAK 2 in Vascular Smooth Muscle Cells Is Dependent on PLD 2
B-RAGE – Mediated Augmentation of Angiotensin II – Induced Activation of JAK 2 in Vascular Smooth Muscle Cells Is Dependent on PLD 2
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发表时间：
2003
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通讯作者：
Seán Shaw;A. Schmidt;A. Banes;Xiaodan Wang;D. Stern;M. Marrero
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作者：
Seán Shaw;A. Schmidt;A. Banes;Xiaodan Wang;D. Stern;M. Marrero
血管紧张素II（Ang II）是一种血管活性肽，也被认为是一种生长因子，与正常和糖尿病细胞增殖有关。我们最近发现Janus激酶2（JAK 2）的激活对于血管紧张素II诱导的血管平滑肌细胞（VSMCs）增殖是必不可少的，并且高糖通过激活JAK 2增加信号转导而增强血管紧张素II诱导的VSMCs增殖。在这里，我们证明，S100 B，晚期糖基化终产物（RAGEs）的受体的配体，增强血管紧张素II诱导的JAK 2的酪氨酸磷酸化和细胞增殖的VSMCs中的受体依赖性的方式。我们还发现，S100 B-ERK相互作用通过激活磷脂酶D（PLD）2触发细胞内活性氧（ROS）的产生、VSMC增殖和JAK 2酪氨酸磷酸化。这些结果为PLD 2、ROS产生和S100 B-Arg诱导的血管紧张素II诱导的细胞增殖增强和VSMC中JAK 2活化之间的联系提供了直接证据。糖尿病52：2381-2388，2003
Angiotensin II (Ang II), a vasoactive peptide that is also considered a growth factor, has been implicated in both normal and diabetic cellular proliferation. We recently found that activation of janus kinase 2 (JAK2) is essential for the Ang II–induced proliferation of vascular smooth muscle cells (VSMCs) and that high glucose augments Ang II–induced proliferation of VSMCs by increasing signal transduction through activation of JAK2. Here, we demonstrate that S100B, a ligand for the receptor of advanced glycation end products (RAGEs), augmented both Ang II–induced tyrosine phosphorylation of JAK2 and cell proliferation in VSMCs in a receptor-dependent manner. We also found that S100B-RAGE interaction triggered intracellular generation of reactive oxygen species (ROS), VSMC proliferation, and JAK2 tyrosine phosphorylation via activation of phospholipase D (PLD)2. These results provide direct evidence for linkages between PLD2, ROS production, and S100B-RAGE–induced enhancement of Ang II–induced cell proliferation and activation of JAK2 in VSMCs. Diabetes 52:2381–2388, 2003