Possible involvement of protein kinase C activation in differentiation of human umbilical vein endothelium-derived cell into smooth muscle-like cell.

We previously reported that when deprived of fibroblast growth factor, human umbilical vein endothelium-derived cells (HUVE-DCs) are capable of differentiating into smooth muscle-like cells through activin A-induced, Smad-dependent signaling, and that maintenance of the endothelial-cell phenotype and differentiation into smooth muscle-like cells are reciprocally controlled by fibroblast growth factor-1 and activin A (Ishisaki et al., 2003). Here, we examined how protein kinase C (PKC), which plays pivotal roles in the regulation of cellular proliferation and differentiation in numerous cell types, might affect the above differentiation. We found that phorbol-12-myristate-13-acetate-induced down-regulations of some PKCs accompany suppressions of the expressions of smooth muscle cell markers in HUVE-DCs deprived of fibroblast growth factor. Moreover, the PKC-inhibitors Gö6850 and Gö6983 suppressed the differentiation of HUVE-DCs into smooth muscle-like cells. These results strongly suggest that activation of PKC is involved in the above differentiation.