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

1)我们之前报道过卵泡抑素促进部分肝切除术后肝脏再生。当进行大面积肝切除术时，残肝的功能至关重要。由于快速生长的细胞缺乏成熟的细胞功能，加速肝细胞生长是否真的有益是一个有趣的问题。为了解决这个问题，我们比较了卵泡抑素和激活素A对90%肝切除大鼠残肝功能的影响。令我们惊讶的是，低剂量的激活素A在残余肝功能方面更有益。2)我们之前报道了激活素A刺激胰腺β细胞再生的功效。然而，激活素A在许多类型的细胞中具有促凋亡作用，这可能是临床应用的一个缺点。因此，我们寻找一种新的因子，它具有激活素样的分化诱导活性，但不促进细胞凋亡。在这方面，我们发现了一种新的长春花生物碱，它可以复制激活素a的作用，但不会诱导细胞凋亡。在体外和体内实验中，茶碱均能有效促进胰腺祖细胞向β细胞分化。

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.