Transdifferentiation-dependent expression of distinct C5a-receptors C5R1 and C5L2 in cultured hepatic stellate cells and their response to C5a-ligand

Background: Recently we reported that the complement factor 5 (C5) is a susceptibility gene for hepatic fibrogenesis in mice and humans (Hillebrandt S et al. Nat Genet 2005). However, the underlying fibrogenic mechanisms of C5 have yet to be defined. Therefore, we initiated the present study with primary cultures of rat hepatic stellate cells (HSC) to analyze the expression of the bona fide receptor C5R1 for the small chemotactic C5a fragment during HSC transdifferentiation in vitro. We also investigated the role of C5L2 during transdifferentiation, in particular since recent studies identified C5L2 as receptor for both C5a and the acylation-stimulating protein (C3adesArg), which is involved in the stimulation of triglyceride synthesis (Kalant D et al. JBC 2005).