Acetylation of HMGB1 by JNK1 Signaling Promotes LPS-Induced Peritoneal Mesothelial Cells Apoptosis
Acetylation of HMGB1 by JNK1 Signaling Promotes LPS-Induced Peritoneal Mesothelial Cells Apoptosis
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JNK1 信号传导对 HMGB1 的乙酰化促进 LPS 诱导的腹膜间皮细胞凋亡
DOI：
10.1155/2018/2649585
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Mao, Haiping
中科院分区：
文献类型：
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作者：
Cao, Shirong;Li, Shu;Mao, Haiping
透析流出液中高迁移率族蛋白1（HMGB 1）的增加与患者腹膜透析相关性腹膜炎和急性腹膜炎小鼠模型中腹膜功能障碍的存在相关，但尚不清楚HMGB 1是否参与腹膜间皮细胞损伤并通过乙酰化进行分子翻译后修饰发挥作用。在此，我们首次发现了患者透析流出物中HMGB 1乙酰化水平与革兰阴性腹膜炎发生之间的相关性。在脂多糖（LPS）处理下，在人腹膜间皮细胞系（HMrSV 5）和小鼠内脏腹膜组织中也观察到乙酰化HMGB 1水平的增加。过表达野生型，但不是hypoacetylation突变体的HMGB 1，增强LPS诱导的HMrSV 5细胞凋亡，这是伴随着升高的蛋白水平的BAX和裂解caspase 3相比，控制。JNK抑制剂预处理HMrSV 5细胞可减弱LPS诱导的HMGB 1乙酰化。与野生型小鼠相比，JNK 1-/-小鼠原代腹膜间皮细胞在LPS刺激后乙酰化HMGB 1蛋白含量降低，凋亡减少，BAX和cleaved-caspase 3蛋白表达降低。总之，我们的数据表明，HMGB 1促进LPS诱导的腹膜间皮细胞凋亡，这与JNK 1介导的HMGB 1乙酰化上调有关。
Increased high mobility group box 1 (HMGB1) in dialysis effluence is associated with the presence of peritoneal dialysis-related peritonitis in patients and peritoneal dysfunction in acute peritonitis mice model, but it remains unclear whether HMGB1 is involved in peritoneal mesothelial cell injury and functions via molecular posttranslational modifications by acetylation in this process. Here we first showed correlation between HMGB1 acetylation level in dialysis effluence of patients and occurrence of Gram-negative peritonitis. The increased level of acetylated HMGB1 was similarly observed under the lipopolysaccharides (LPS) treatment in both human peritoneal mesothelial cell line (HMrSV5) and mice visceral peritoneum tissue. Overexpression of wild-type, but not hypoacetylation mutant of HMGB1, enhanced LPS-induced apoptosis in HMrSV5 cells, which was accompanied by elevated protein levels of BAX and cleaved-caspase 3 compared to the control. Pretreatment of HMrSV5 cell with JNK inhibitor attenuated LPS-induced HMGB1 acetylation. Consistently, primary peritoneal mesothelial cells from Jnk1-/- mice showed a lower protein contents of acetylated HMGB1, fewer apoptosis, and decreased protein expression of BAX and cleaved-caspase3 after LPS exposure, as compared to those from wild-type mice. In conclusion, our data demonstrated HMGB1 promotes LPS-induced peritoneal mesothelial cells apoptosis, which is associated with JNK1-mediated upregulation of HMGB1 acetylation.