Inhibition of transient receptor potential melastain 7 channel increases HSCs apoptosis induced by TRAIL

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• 作者：Hong Liu ; Jun Li ; ^{lijun@ahmu.edu.cn} ; Yan Huang ; Cheng Huang
• 关键词：Transient receptor potential melastain 7 ; Hepatic stellate cells ; Hepatic fibrosis ; TNF-related apoptosis inducing-ligand ; Apoptosis ; TRPM7 inhibitors
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：20 April, 2012
• 卷：90
• 期：15-16
• 页码：612-618
• 文件大小：738 K

摘要

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.