Generation of insulin-producing cells from the mouse liver using β cell-related gene transfer including Mafa and Mafb.
Generation of insulin-producing cells from the mouse liver using β cell-related gene transfer including Mafa and Mafb.
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DOI：
10.1371/journal.pone.0113022
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Takahashi S
中科院分区：
文献类型：
--
作者：
Nagasaki H;Katsumata T;Oishi H;Tai PH;Sekiguchi Y;Koshida R;Jung Y;Kudo T;Takahashi S
最近对大Maf转录因子的研究表明，Mafb和Mafa在β细胞发育和成熟中具有各自独特的作用。然而，这种作用上的差异是由于基因表达的时间（大致上，Mafb在出生前表达，Mafa在出生后表达）还是由于每个基因的特定功能尚不清楚。我们的目的是通过使用β样细胞生成的体内模型来检查这些与β细胞密切相关的基因之间的功能差异。我们通过测量胰岛素启动子-荧光素酶转基因（MIP-Luc-VU）小鼠肝脏发出的生物发光来监测胰岛素基因转录。腺病毒基因转移的Pdx 1/Neurod/Mafa（PDA）和Pdx 1/Neurod/Mafb（PDB）组合产生强烈的发光从肝脏持续超过1周，并在转导后3天达到峰值。PDA和PDB的峰信号强度相当。然而，PDA而不是PDB转移导致在第10天显著的生物发光，表明Mafa在胰岛素基因激活中比Mafb具有更可持续的作用。PDA和PDB转移改善链脲佐菌素（STZ）诱导的糖尿病模型中的葡萄糖水平分别长达21天和7天。此外，PDA转移诱导了第9天肝脏中葡萄糖传感和胰岛素分泌所必需的几种基因表达。然而，葡萄糖耐量试验和肝脏灌注实验未显示葡萄糖刺激的肝内β样细胞的胰岛素分泌。这些结果表明，MIP-Luc-VU小鼠中的生物发光成像提供了检测肝脏中β样细胞的非侵入性手段。它们还表明，与Mafb相比，Mafa在β样细胞产生中具有显著强烈和持续的作用。
Recent studies on the large Maf transcription factors have shown that Mafb and Mafa have respective and distinctive roles in β-cell development and maturation. However, whether this difference in roles is due to the timing of the gene expression (roughly, expression of Mafb before birth and of Mafa after birth) or to the specific function of each gene is unclear. Our aim was to examine the functional differences between these genes that are closely related to β cells by using an in vivo model of β-like cell generation. We monitored insulin gene transcription by measuring bioluminescence emitted from the liver of insulin promoter-luciferase transgenic (MIP-Luc-VU) mice. Adenoviral gene transfers of Pdx1/Neurod/Mafa (PDA) and Pdx1/Neurod/Mafb (PDB) combinations generated intense luminescence from the liver that lasted for more than 1 week and peaked at 3 days after transduction. The peak signal intensities of PDA and PDB were comparable. However, PDA but not PDB transfer resulted in significant bioluminescence on day 10, suggesting that Mafa has a more sustainable role in insulin gene activation than does Mafb. Both PDA and PDB transfers ameliorated the glucose levels in a streptozotocin (STZ)-induced diabetic model for up to 21 days and 7 days, respectively. Furthermore, PDA transfer induced several gene expressions necessary for glucose sensing and insulin secretion in the liver on day 9. However, a glucose tolerance test and liver perfusion experiment did not show glucose-stimulated insulin secretion from intrahepatic β-like cells. These results demonstrate that bioluminescence imaging in MIP-Luc-VU mice provides a noninvasive means of detecting β-like cells in the liver. They also show that Mafa has a markedly intense and sustained role in β-like cell production in comparison with Mafb.
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影响因子：
4.8
作者：
Shao, Chunli;Cobb, Melanie H.
通讯作者：
Cobb, Melanie H.
DOI：
10.1073/pnas.86.20.7711
发表时间：
1989-10-01
影响因子：
11.1
作者：
NISHIZAWA, M;KATAOKA, K;KAWAI, S
通讯作者：
KAWAI, S
影响因子：
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作者：
Horb, ME;Shen, CN;Slack, JMW
通讯作者：
Slack, JMW
胰腺内的细胞可塑性 - 不从发育中学到的。
影响因子：
11.8
作者：
Puri, Sapna;Hebrok, Matthias
通讯作者：
Hebrok, Matthias
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.