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Mechanism of differentiation and growth of pancreatic βcells by newly identified growth factor, NTAK, and its application for regenerative medicine in diabetes mellitus

新发现的生长因子NTAK诱导胰腺β细胞分化和生长的机制及其在糖尿病再生医学中的应用

基本信息

批准号：
18591006
负责人：
MIYAGAWA Jun-ichiro
金额：
$ 2.18万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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-18591006/
关键词：
NTAK Pancreatic β cell growth factor proliferation differentiation development regeneration diabetes mellitus

项目摘要

We have been studied on the mechanism of regeneration and differentiation, and apoptosis of pancreatic β cells to develop the new therapeutic approach to diabetes mellitus. In this research, we investigated the possible involvement of neural-and thymus-derived activator for ErbB kinases (NTAK), newly identified growth factor which belongs to the EGF family, and CD 9, one of the modulators of EGF family signal transduction. We demonstrated the adult and fetal pancreas produced NTAK which is localized in β cells and fetal pancreatic epithelial cells including endocrine precursor cells, respectively. CD-9 also expressed on islet cells. These results suggested that NTAK and CD-9 may be involved in the mechanism of differentiation and/or proliferation of pancreatic β cells in addition to the development of pancreas.In vitro peptide study of NTAK revealed that partial sequence of peptides of NTAK showed the activity of proliferation, while some other part of peptide sequence inhibited the proliferation of β cell line, MIN6 cells, suggesting that NTAK signal transduction may be involved in both positive and negative (apoptotic?) regulatory pathways for β cell proliferation and/or differentiation. Further study is necessary to elucidate the detailed signal transduction pathway(s) of NTAK in pancreatic β cells.

我们对胰腺β细胞的再生、分化和凋亡机制进行了研究，以开发糖尿病治疗的新途径。在这项研究中，我们研究了神经和胸腺衍生的ErbB激酶激活剂（NTAK），新发现的生长因子，属于EGF家族，和CD 9，EGF家族信号转导的调节剂之一的可能参与。我们证明成人和胎儿胰腺产生NTAK，其分别定位于β细胞和胎儿胰腺上皮细胞，包括内分泌前体细胞。CD-9也在胰岛细胞上表达。NTAK的体外肽段研究表明，NTAK的部分肽段具有增殖活性，而部分肽段对β细胞株MIN 6细胞的增殖有抑制作用。这表明NTAK信号转导可能参与了阳性和阴性（凋亡？）细胞增殖和/或分化的调节途径。需要进一步研究以阐明NTAK在胰腺β细胞中的详细信号转导途径。