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

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.