HMGB1-induced angiogenesis in perforated disc cells of human temporomandibular joint.
HMGB1-induced angiogenesis in perforated disc cells of human temporomandibular joint.
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HMGB1诱导人颞下颌关节穿孔盘细胞血管生成
DOI：
10.1111/jcmm.13410
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Long X
中科院分区：
文献类型：
--
作者：
Feng Y;Ke J;Cao P;Deng M;Li J;Cai H;Meng Q;Li Y;Long X
高迁移率族1蛋白（HMGB 1）是一种高度保守的核DNA结合蛋白和炎症介质，最近被发现参与血管生成。我们的前期研究已经证实了HMGB 1在颞下颌关节盘（TMJ）穿孔组织中的表达升高。在此，我们研究了HMGB 1在调节低氧诱导因子-1 α（HIF-1α）和血管内皮生长因子（VEGF）介导TMJ穿孔盘细胞血管生成中的新介质。HMGB 1以剂量和时间依赖性方式增加这些细胞中HIF-1α和VEGF的表达。免疫荧光检测显示HMGB 1可激活HIF-1α。此外，在这些细胞中，HMGB 1激活细胞外信号相关激酶1/2（Erk 1/2），Jun N末端激酶（JNK），但不激活P38。此外，U 0126（ErK抑制剂）和SP 600125（JNK抑制剂）均显著抑制HMGB 1诱导的HIF-1α和VEGF的产生。暴露于HMGB 1刺激的穿孔盘细胞衍生的条件培养基可显著增加人脐静脉内皮细胞（HUVECs）的管形成，而单独使用VEGF、HIF-1α、Erk和JNK抑制剂预处理则可减弱。因此，丰富的HMGB 1通过Erk和JNK途径介导椎间盘细胞中HIF-1α的活化，然后启动VEGF分泌，从而导致椎间盘血管生成并加速穿孔椎间盘的退行性变化。
High mobility group 1 protein (HMGB1), a highly conserved nuclear DNA‐binding protein and inflammatory mediator, has been recently found to be involved in angiogenesis. Our previous study has demonstrated the elevation of HMGB1 in the tissue of perforated disc of temporomandibular joint (TMJ). Here, we investigated a novel mediator of HMGB1 in regulating hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF) to mediate angiogenesis in perforated disc cells of TMJ. HMGB1 increased the expression of HIF‐1α and VEGF in a dose‐ and time‐dependent manner in these cells. Moreover, immunofluorescence assay exhibits that the HIF‐1α were activated by HMGB1. In addition, HMGB1 activated extracellular signal‐related kinase 1/2 (Erk1/2), Jun N‐terminal kinase (JNK), but not P38 in these cells. Furthermore, both U0126 (ErK inhibitor) and SP600125 (JNK inhibitor) significantly suppressed the enhanced production of HIF‐1α and VEGF induced by HMGB1. Tube formation of human umbilical vein endothelial cells (HUVECs) was significantly increased by exposure to conditioned medium derived from HMGB1‐stimulated perforated disc cells, while attenuated with pre‐treatment of inhibitors for VEGF, HIF‐1α, Erk and JNK, individually. Therefore, abundance of HMGB1 mediates activation of HIF‐1α in disc cells via Erk and JNK pathway and then, initiates VEGF secretion, thereby leading to disc angiogenesis and accelerating degenerative change of the perforated disc.
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影响因子：
29.4
作者：
Kang R;Zhang Q;Hou W;Yan Z;Chen R;Bonaroti J;Bansal P;Billiar TR;Tsung A;Wang Q;Bartlett DL;Whitcomb DC;Chang EB;Zhu X;Wang H;Lu B;Tracey KJ;Cao L;Fan XG;Lotze MT;Zeh HJ 3rd;Tang D
通讯作者：
Tang D
影响因子：
10.6
作者：
Kang, Rui;Chen, Ruochan;Zhang, Qiuhong;Hou, Wen;Wu, Sha;Cao, Lizhi;Huang, Jin;Yu, Yan;Fan, Xue-gong;Yan, Zhengwen;Sun, Xiaofang;Wang, Haichao;Wang, Qingde;Tsung, Allan;Billiar, Timothy R.;Zeh, Herbert J., III;Lotze, Michael T.;Tang, Daolin
通讯作者：
Tang, Daolin
影响因子：
4.6
作者：
Biscetti, F.;Flex, A.;Ferraccioli, G.
通讯作者：
Ferraccioli, G.
影响因子：
2.8
作者：
Miller, Daniel;DeSutter, Christopher;Bray, Robert C.
通讯作者：
Bray, Robert C.
影响因子：
2
作者：
Loreto, C.;Almeida, L. E.;Leonardi, R.
通讯作者：
Leonardi, R.