THE MITOGENIC EFFECT OF PLATELET-DERIVED GROWTH-FACTOR IN HUMAN HEPATIC STELLATE CELLS REQUIRES CALCIUM INFLUX

Platelet-derived growth factor (PDGF) is a key mitogen for hepatic ste llate cells (HSC) and has been shown to be implicated in liver tissue repair and fibrogenesis. In this study the relationship between PDGF-i nduced intracellular Ca2+ concentration ([Ca2+](i)) increase and mitog enesis in cultured human HSC was evaluated. In high-density cell cultu res (80-90% subconfluence), PDGF induced a significant increase in [Ca 2+](i), characterized by a short-lasting peak phase, which was followe d by a long-lasting plateau phase. The plateau phase was abolished in the absence of extracellular Ca2+. However, in low-density cell cultur es (30-40% subconfluence), the plateau phase was absent or markedly le ss pronounced. In parallel sets of experiments, PDGF was significantly less effective in inducing mitogenesis in low-density cell cultures t han in high-density cell cultures and was totally ineffective in the a bsence of extracellular Ca2+. These results suggest that 1) spatial an d time dynamics of PDGF-induced [Ca2+](i) increase are dependent on ce ll density and 2) PDGF-induced mitogenesis requires extracellular Ca2 influx.