Inhibition of transient receptor potential melastain 7 channel increases HSCs apoptosis induced by TRAIL
Inhibition of transient receptor potential melastain 7 channel increases HSCs apoptosis induced by TRAIL
复制标题
抑制瞬时受体电位melastin 7通道增加TRAIL诱导的HSC凋亡
DOI：
10.1016/j.lfs.2012.02.012
复制
发表时间：
2012-04-20
期刊：
影响因子：
6.1
通讯作者：
Huang, Cheng
中科院分区：
文献类型：
--
作者：
Liu, Hong;Li, Jun;Huang, Cheng
目的：瞬时受体电位黑色素蛋白7（TRPM 7）通道在多种细胞过程和多种疾病的病理学中具有重要作用。本研究旨在探讨TRPM 7与肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis inducing-ligand，TRAIL）诱导的肝星状细胞（hepatic stellate cells，HSC）凋亡的关系。在这项研究中，使用Western印迹，RT-PCR和流式细胞术分析相结合，我们研究了TRPM 7通道对TRAIL诱导的HSC凋亡的影响及其潜在功能，HSC是细胞外基质（ECM）形成的关键细胞。结论：TRPM 7基因在肝星状细胞中有表达，TRPM 7基因在肝星状细胞中的表达与肝纤维化的发生密切相关，TRPM 7基因在肝星状细胞中的表达与肝纤维化的发生密切相关。用2-氨基乙氧基二苯基硼酸盐（2-APB）或Gd ~（3+）抑制TRPM 7通道不仅能显著抑制TRPM 7的表达，而且能增加TRAIL诱导的HSC凋亡，提示TRPM 7通道可能通过调节HSC对TRAIL的敏感性参与TRAIL诱导的HSC凋亡。(c)2012 Elsevier Inc. All rights reserved.
Aims: Transient receptor potential melastain 7 (TRPM7) channels are known to have a fundamental role in many cellular processes and pathology of various diseases. The objective of this study was to investigate the potential relationship between TRPM7 and the apoptosis of hepatic stellate cells (HSCs) induced by TNF-related apoptosis inducing-ligand (TRAIL).Main methods: In this study, using a combination of Western blotting, RT-PCR and flow cytometric analysis, we investigated the influence and potential function of TRPM7 channels on the apoptosis induced by TRAIL in HSCs which is the key cell of formation of extracellular matrix (ECM) and is also the core link of occurrence of hepatic fibrosis (HF).Key findings: We observed significant expression of TRPM7 mRNA and protein in HSCs. Suppression of TRPM7 channels by 2-aminoethoxydiphenyl borate (2-APB) or Gd3+ not only markedly eliminated TRPM7 expression, but also increased the apoptosis of HSCs induced by TRAIL a major apoptosis stimulator of HSCs.Significance: Our findings strongly suggest that TRPM7 channels are involved in the apoptosis of HSCs induced by TRAIL, probably by regulating the sensitivity of HSCs to TRAIL. (c) 2012 Elsevier Inc. All rights reserved.