The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells
The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells
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高迁移率族盒 1 蛋白在白细胞介素 18 诱导的瓣膜间质细胞肌纤维母细胞转变中的作用
作者：
Xianming Zhou;Hua Xiao;Nianguo Dong;Fei Li
背景：钙化主动脉瓣病（CAVD）患者中白细胞介素-18 （IL-18）和高迁移率组盒1蛋白（HMGB1）水平升高已被报道。然而，IL-18和HMGB1在调节瓣膜间质细胞（VIC）表型中的作用尚不清楚。我们假设HMGB1介导il -18诱导的vic肌成纤维转变。方法：采用免疫组化染色、实时聚合酶链反应和免疫印迹法检测人主动脉瓣组织中IL-18、HMGB1和α-平滑肌肌动蛋白（α-SMA）的表达。采用ELISA试剂盒检测血浆IL-18和HMGB1浓度。以体外培养的人主动脉内皮细胞为模型。结果：免疫组化、免疫印迹显示钙化瓣膜组织中IL-18、HMGB1、α-SMA水平升高。循环IL-18和HMGB1水平在CAVD患者中也较高。IL-18在体外诱导VICs中HMGB1和α-SMA表达上调。此外，IL-18诱导HMGB1分泌到细胞外空间并激活核因子κ b （NF-κB）。阻断NF-κB可消除IL-18诱导的HMGB1的上调和释放。抑制HMGB1可减弱IL-18诱导的α-SMA表达，而增强IL-18的作用。结论：我们首次证明了CAVD患者组织和血浆中IL-18和HMGB1水平升高。机械上，HMGB1介导il -18诱导VIC肌成纤维转化。
Background: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. Methods: The expression of IL-18, HMGB1 and α-smooth muscle actin (α-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting. Plasma concentrations of IL-18 and HMGB1 were measured using the ELISA kit. Cultured human aortic VICs were used as an in vitro model. Results: Immunohistochemistry and immunoblotting revealed increased levels of IL-18, HMGB1 and α-SMA in calcific valves. Circulating IL-18 and HMGB1 levels were also higher in CAVD patients. In vitro, IL-18 induced upregulation of HMGB1 and α-SMA in VICs. Moreover, IL-18 induced secretion of HMGB1 to the extracellular space and activation of nuclear factor kappa-B (NF-κB). Blockade of NF-κB abrogated the upregulation and release of HMGB1 induced by IL-18. Whereas HMGB1 inhibition attenuated the IL-18-induced expression of α-SMA, HMGB1 enhanced the effect of IL-18. Conclusions: We demonstrated for the first time that both tissue and plasma levels of IL-18 and HMGB1 were increased in patients with CAVD. Mechanically, HMGB1 mediated IL-18-induced VIC myofibroblastic transition.
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DOI：
10.1152/ajpheart.01285.2008
发表时间：
2009-07-01
影响因子：
4.8
作者：
Yu, Qianli;Vazquez, Randy;Larson, Douglas F.
通讯作者：
Larson, Douglas F.
高迁移率group box-1蛋白诱导主动脉瓣间质细胞成骨表型变化
DOI：
10.1016/j.jtcvs.2015.09.077
发表时间：
2016-01-01
影响因子：
6
作者：
Wang, Bo;Li, Fei;Dong, Nianguo
通讯作者：
Dong, Nianguo
DOI：
--
发表时间：
2008
期刊：
The Journal of heart valve disease
影响因子：
--
作者：
J. Butcher;C. Simmons;J. Warnock
通讯作者：
J. Butcher;C. Simmons;J. Warnock
影响因子：
168.9
作者：
Nkomo, Vuyisile T.;Gardin, Julius M.;Enriquez-Sarano, Maurice
通讯作者：
Enriquez-Sarano, Maurice
影响因子：
3.4
作者：
Tan, Yonghong;Wang, Qiong;Zhao, Baisong
通讯作者：
Zhao, Baisong