Establishment of Therapeutic Approaches by Modification of the Activin-Follistatin System.

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1) We previously reported that follistatin accelerates liver regeneration after partial hepatectomy. When massive hepatectomy is performed, the function of the remnant liver is critical. Since rapidly growing cells lack mature cell functions, it is an interesting question whether or not acceleration of hepatocyte growth is actually beneficial. To address this issue, we compared the effect of follistatin and activin A on remnant liver function in 90% hepatectomized rats. To our surprise, administration of low dose of activin A was more beneficial in terms of remnant liver function.2) We previously reported the efficacy of activin A in stimulating regeneration of pancreatic beta cells. However, activin A has a proapoptotic action in many types of cells, which may be a disadvantage for clinical use. We therefore searched for a new factor which has an activin-like differentiation-inducing activity without promoting apoptosis. In this regard, we found conophylline, a new vinca alkaloid, which reproduces the action of activin A but does not induce apoptosis. Conophylline was effective in promoting differentiation of pancreatic progenitors to beta cells in vitro and in vivo.