Morphological study of endothelin-1-induced contraction of cultured hepatic stellate cells on hydrated collagen gels.

Hepatic stellate cells become activated and aquire contractility on being cultured. In order to characterize the morphology of contracted and relaxed stellate cells, we performed light- and electron-microscopic analyses of cultured stellate cells on collagen gels. Incubation of stellate cells with medium alone, 10 nM endothelin (ET)-1, or 1 mM N6,2' dibutyryladenosine 3':5'-cyclic monophosphate (dBcAMP) for 48 h induced contraction of the underlying collagen gels to 83%, 57%, and 97%, respectively, of their original size. Stellate cells relaxed by dBcAMP exhibited a round cell body and extended several long thin cytoplasmic processes with several varicosities. Culture with ET-1 accelerated spreading of the stellate cells on collagen gels and decreased the number of processes. Each such flattened stellate cell attached itself to the underlying collagen matrix by bending its cell body. Collagen fibers around the cell were pulled toward the cell and stretched. Thus, the present study has revealed that ET-1-stimulated cultured stellate cells adduct associated collagen fibers by the retraction of cytoplasmic processes and the bending of their spread cell bodies.