Host: The 93rd Annual Meeting of the Japanese Pharmacological Society
Name : The 93rd Annual Meeting of the Japanese Pharmacological Society
Number : 93
Location : Yokohama
Date : March 16, 2020 - March 18, 2020
Hepatic stellate cells are liver-specific pericytes that play central roles in the development of liver fibrosis. During liver injury, hepatic stellate cells transdifferentiate from the quiescent phenotype into the myofibroblast-like phenotype, resulting in high proliferation and extracellular matrix production. Large-conductance Ca2+-activated K+ (BKCa) channels are expressed in many types of tissues and involved in the regulation of membrane potential, intracellular Ca2+ concentration, and cell proliferation. However, the involvement of BKCa channels on liver fibrosis remains unclear. In this study, we investigated the pathophysiological roles of BKCa channels in a human hepatic stellate cell line, LX-2. The mRNA expression analysis revealed that LX-2 cells highly expressed the α subunit of BKCa channels. In LX-2 cells, extracellular Ca2+ restoration in the presence of thapsigargin induced store-operated Ca2+ (SOC) entry, which potentially mediated by Orai/STIM channels. The SOC entry was significantly reduced by a specific inhibitor of BKCa channels, paxilline. In addition, the proliferation of LX-2 cells was clearly attenuated by paxilline. These results suggest that BKCa channels are functionally expressed in LX-2 cells and contribute to cell proliferation by regulating intracellular Ca2+ signaling.
