JNK-ATF-2 通过募集组蛋白去乙酰化酶 4（HDAC4）并在血栓调节蛋白（TM）启动子上形成转录抑制复合物来抑制 TM 的表达。

JNK-ATF-2 inhibits thrombomodulin (TM) expression by recruiting histone deacetylase4 (HDAC4) and forming a transcriptional repression complex in the TM promoter.

机构信息

The key laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong, China.

出版信息

FEBS Lett. 2010 Mar 5;584(5):852-8. doi: 10.1016/j.febslet.2010.01.048. Epub 2010 Jan 30.

DOI:10.1016/j.febslet.2010.01.048

PMID:20116378

Abstract

Thrombomodulin (TM) is an important vascular protective molecule that has anticoagulant, anti-inflammatory and anti-apoptotic properties. TM is downregulated in many thrombotic and vascular diseases. However, the mechanisms responsible for TM suppression are not completely understood. In this study, we investigated the mechanism involved in fatty acid-induced suppression of TM expression in human aortic endothelial cells. We found that palmitic acid inhibited TM expression through the JNK and p38 pathways. ATF-2, a JNK and p38 target transcription factor, was involved in the suppression. ATF-2 can bind to the TM promoter, recruit HDAC4 and form a transcriptional repression complex in the promoter, which may lead to chromatin condensation and transcriptional arrest. This study provides novel insight into TM down-regulation by stress signaling pathways.

摘要

血栓调节蛋白（TM）是一种重要的血管保护分子，具有抗凝、抗炎和抗凋亡作用。TM 在许多血栓形成和血管疾病中下调。然而，导致 TM 抑制的机制尚不完全清楚。在这项研究中，我们研究了脂肪酸诱导人主动脉内皮细胞 TM 表达抑制的机制。我们发现，软脂酸通过 JNK 和 p38 途径抑制 TM 的表达。ATF-2，JNK 和 p38 的靶转录因子，参与了抑制。ATF-2 可以与 TM 启动子结合，招募 HDAC4 并在启动子中形成转录抑制复合物，这可能导致染色质凝聚和转录停滞。这项研究为应激信号通路下调 TM 提供了新的见解。