Activin A induces terminal differentiation of cultured human keratinocytes

Activin A, a member of the TGF beta-superfamily, is well known to play important roles in the growth and differentiation of various target cells. We have previously demonstrated that activin A is produced at an early stage of cultivation at both the protein and the mRNA levels in cultured human keratinocytes. In this study, the effects of activin A on differentiation and proliferation of human keratinocytes were examined. Activin A (greater than or equal to 1 nM) induced cornified envelope-formation and the synthesis of loricrin, keratin 1, involucrin, and transglutaminase 1. In addition, transglutaminase activity and mRNA level of transglutaminase 1 were increased by activin A. [H-3] Thymidine incorporation and cell number were reduced by activin A (greater than or equal to 1 nM) compared with control, suggesting an inhibitory effect of activin A on cell proliferation. On the basis of these findings, it is likely that activin A contributes to differentiation and suppression of proliferation in human keratinocytes.