Role of Pax4/Pax6 in pancreatic β-cell differentiation and maintaining its function

Pax4/Pax6 在胰腺 β 细胞分化和维持其功能中的作用

• 批准号: 14370335
• 负责人: YAMASAKI Yoshimitsu
• 金额: $ 5.95万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370335/
• 关键词: PAX4; PAX6; transcription factor; β-cell differentiation; pancreas; development; transdifferentiation; diabetes

Pax4 is well known to play some important role in pancreas development. In our study, we showed that Pax4 overexpression induces differentiation from precursor cells to insulin-producing cells. Various β-cell-specific factors including GLUT2 were also induced by Pax4 overexpression, indicating that Pax4 facilitates p-cell differentiation. In addition, we showed that Pax4 functions as a transcriptional repressor and found several candidate molecules which binds to Pax4 and could function as a co-repressor of Pax4.Also, we found that Pax6 plays some important role in maintaining β-cell function; we showed that in Pax6 (+/-) mice glucose-stimulated insulin secretion was impaired, although there was no difference in pancreas morphology and insulin content. These results indicate that Pax6 plays some important role in glucose-stimulated insulin secretion.

众所周知，Pax4在胰腺发育中起着重要作用。在我们的研究中，我们发现Pax4的过度表达可以诱导前体细胞向胰岛素分泌细胞分化。Pax4过表达还诱导了包括GLUT2在内的多种β细胞特异性因子的表达，表明Pax4促进了p细胞的分化。此外，我们还发现了Pax4作为转录抑制因子的功能，并发现了几个与Pax4结合的候选分子可以作为Pax4的辅助抑制因子。此外，我们还发现Pax6在维持β细胞功能方面发挥着重要的作用；我们发现在Pax6(+/-)小鼠中，葡萄糖刺激的胰岛素分泌受到了抑制，尽管在胰腺形态和胰岛素含量方面没有差异。这些结果表明，Pax6在葡萄糖刺激的胰岛素分泌中起着重要作用。

项目成果

Kawamori D, et al.: "Oxidative Stress Induces Nucleo-Cytoplasmic Translocation of Pancreatic Transcription Factor PDX-1 Through Activation of c-Jun NH(2)-terminal Kinase"Diabetes. 52(12). 1896-1904 (2003)

Kawamori D 等人：“氧化应激通过 c-Jun NH(2)-末端激酶的激活诱导胰腺转录因子 PDX-1 的核细胞质易位”糖尿病。

Yoshida S, et al.: "PDX-l Induces Differentiation of Intestinal Epitheloid IEC-6 into Insulin-Producing Cells"Diabetes. 51(8). 2505-213 (2002)

Yoshida S 等人：“PDX-1 诱导肠上皮样 IEC-6 分化为胰岛素产生细胞”糖尿病。

Fujitani Y, et al.: "Identification of a portable repression domain and an ElA-responsive activation domain in pax4 : a possible role of pax4 as a transcription al repressor in the pancreas."Molecular and Cellular Biology. 19(12). 8281-8291 (1999)

Fujitani Y 等人：“pax4 中便携式抑制结构域和 ElA 响应激活结构域的鉴定：pax4 作为胰腺中转录抑制因子的可能作用。”分子和细胞生物学。

Yasuda T, et al.: "PAX6 mutation as a genetic factor common to aniridia and glucose intolerance"Diabetes. 51(1). 224-230 (2002)

Yasuda T 等人：“PAX6 突变是无虹膜和葡萄糖耐受不良的常见遗传因素”糖尿病。

Kaneto H, et al.: "Oxidative stress induces p21 expression in pancreatic islet cell : possible Implication in beta-cell dysfunction"Diabetologia. 42(9). 1093-1097 (1999)

Kaneto H 等人：“氧化应激诱导胰岛细胞中的 p21 表达：可能对 β 细胞功能障碍有影响”Diabetologia。