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

通过修改激活素-卵泡抑素系统建立治疗方法。

• 批准号: 18390273
• 负责人: KOJIMA Itaru
• 金额: $ 11.07万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390273/
• 关键词: activin; follistatin; diabetes; fibrosis; regeneration; 細胞増殖; 分化; 肝再生; 血管新生; 血管内皮; 管腔形成

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.

1)我们以前报道过卵泡抑素可以加速部分肝切除术后的肝再生。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，这是一个有趣的问题，加速肝细胞生长是否真的有益。为了解决这个问题，我们比较了卵泡抑素和激活素A对90%肝切除大鼠残余肝功能的影响。令我们惊讶的是，给予低剂量的激活素A在残余肝功能方面更有益。2）我们先前报道了激活素A在刺激胰腺β细胞再生中的功效。然而，激活素A在许多类型的细胞中具有促凋亡作用，这可能是临床使用的缺点。因此，我们寻找一种新的因子，它具有激活素样分化诱导活性，而不促进细胞凋亡。在这方面，我们发现了一种新的长春花生物碱，即Conophylline，它能复制激活素A的作用，但不诱导细胞凋亡。体外和体内实验表明，茶碱可有效促进胰腺祖细胞向β细胞分化。

项目成果

Effect of Extracellular Matrix on Differentiation of AR42J Cells

细胞外基质对AR42J细胞分化的影响

• 发表时间: 2007
• 作者: Hamamoto;K.;Yamada;S.;Yamamoto;Y.;Kodera;K.;Hara;A.;Seno;M.;Kojima;I.
• 通讯作者: I.

Treatment of Type 2 Diabetes By Transduction of BTC Gene

BTC基因转导治疗2型糖尿病

• 发表时间: 2007
• 作者: Yamamoto;Y.;Yamada;S.;Kodera;T.;Hara;A.;Tanaka;Y.;Motoyoshi;K.;Seno;M.;Kojima;I.
• 通讯作者: I.

Establishment of Organ Culture System to Analyze the Formation of the Mantle-core Structure

建立器官培养系统分析幔核结构的形成

• 发表时间: 2007
• 作者: Hara;A.;Yamada;S.;Yamamoto;Y.;Kodera;T.;Kojima;I.
• 通讯作者: I.

Activin in Diabetes. Retinopathy

糖尿病中的激活素。

• 发表时间: 2007
• 作者: Maeshima;K.;Takahashi;K.;Kishi;A.;Kojima;I.
• 通讯作者: I.

糖尿病再生医療の現状と未来

糖尿病再生医学的现状与未来

• 发表时间: 2006
• 期刊: 糖尿病学の進歩 40
• 作者: 山本頼綱;小島至
• 通讯作者: 小島至