The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells.

The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells.
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DOI:
10.1083/jcb.152.6.1197
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发表时间:
2001-03-19
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Bianchi ME
Bianchi ME
中科院分区:
其他
文献类型:
--
作者:
Degryse B;Bonaldi T;Scaffidi P;Müller S;Resnati M;Sanvito F;Arrigoni G;Bianchi ME

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HMG1(高迁移率组1)是一种普遍存在且丰富的染色质成分。然而,HMG1可由活化的巨噬细胞和单核细胞分泌,并可作为炎症和内毒素致死的介质。在这里,我们记录了细胞外HMG1在细胞迁移中的作用。HMG1(及其单个dna结合域)在趋化性、趋化运动和伤口愈合实验中刺激大鼠平滑肌细胞的迁移。HMG1诱导细胞形状快速和短暂的改变,肌动蛋白细胞骨架重组导致运动细胞典型的细长极化形态。这些作用被针对晚期糖基化终产物受体的抗体所抑制,这表明晚期糖基化终产物受体是介导hmg1依赖性迁移反应的受体。百日毒和丝裂原活化蛋白激酶激酶抑制剂PD98059也阻断了HMG1诱导的大鼠平滑肌细胞迁移,提示Gi/o蛋白和丝裂原活化蛋白激酶是HMG1信号通路所必需的。我们还发现HMG1可以通过多种细胞类型的损伤或坏死释放,包括内皮细胞。因此,HMG1具有促进血管损伤后动脉粥样硬化和再狭窄分子的所有特征。
HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a Gi/o protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage.
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