活性化型肝星細胞におけるカルシウム感受性受容体（CASR）の機能発現

抄録

Hepatic stellate cells (HSC) are liver-specific fibroblasts that play a critical role in the development of hepatic fibrosis. During liver injury, these cells transdifferentiate into the activated phenotype, resulting in enhanced cell proliferation and extracellular matrix production. The functions of activated HSCs require an increase in cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt). However, the regulatory mechanisms underlying Ca²⁺ signaling in activated HSCs remain largely unknown. In the present study, the pathophysiological roles of calcium sensing receptors (CaSRs) were examined in human hepatic stellate cells LX-2. Expression analyses revealed that CaSR proteins were expressed in α-smooth muscle actin-positive LX-2 cells. Extracellular Ca²⁺ restoration (from 0 to 2.2 mM) increased [Ca²⁺]_cyt in LX-2 cells. The extracellular Ca²⁺-induced increase in [Ca²⁺]_cyt was reduced by the CaSR antagonists, 10µM NPS2143 and Calhex 231.TGF-β1 caused the upregulation of myofibroblast markers, α-SMA and Col1α1, in LX-2 cells. This upregulation was markedly reduced by NS2143. The treatment with NS2143 and Calhex 231 significantly attenuated the proliferation of LX-2 cells. These results indicate that CaSRs are functionally expressed in hepatic stellate cells and contribute to extracellular matrix production and cell proliferation.