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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MafB is required for islet β cell maturation
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MafB is required for islet β cell maturation

机译：MafB是胰岛β细胞成熟所必需的

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摘要

Pancreatic endocrine cell differentiation depends on transcription factors that also contribute in adult insulin and glucagon gene expression. Islet cell development was examined in mice lacking MafB, a transcription factor expressed in immature α (glucagon~+) and β (insulin~+) cells and capable of activating insulin and glucagon expression in vitro. We observed that MafB~(-/-) embryos had reduced numbers of insulin~+ and glucagon~+ cells throughout development, whereas the total number of endocrine cells was unchanged. Moreover, production of insulin~+ cells was delayed until embryonic day (E) 13.5 in mutant mice and coincided with the onset of MafA expression, a MafB-related activator of insulin transcription. MafA expression was only detected in the insulin~+ cell population in MafB mutants, whereas many important regulatory proteins continued to be expressed in insulin~- β cells. However, Pdx1, Nkx6.1, and GLUT2 were selectively lost in these insulin-deficient cells between E15.5 and E18.5. MafB appears to directly regulate transcription of these genes, because binding was observed within endogenous control region sequences. These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature α and β cells.
机译：胰腺内分泌细胞的分化取决于转录因子，而转录因子也有助于成人胰岛素和胰高血糖素基因的表达。在缺乏MafB的小鼠中检查了胰岛细胞的发育，MafB是在未成熟的α（胰高血糖素+）和β（胰岛素+）细胞中表达的转录因子，能够在体外激活胰岛素和胰高血糖素的表达。我们观察到，在整个发育过程中，MafB〜（-/-）胚胎的胰岛素〜和胰高血糖素〜+细胞数量减少，而内分泌细胞总数没有变化。此外，胰岛素+细胞的产生被推迟到突变小鼠的胚胎天（E）13.5为止，并且与MafA表达的开始相吻合，MafA表达是MafB相关的胰岛素激活因子。仅在MafB突变体的胰岛素+细胞群体中检测到MafA表达，而许多重要的调节蛋白仍在胰岛素-β细胞中表达。但是，Pdx1，Nkx6.1和GLUT2在E15.5和E18.5之间的这些胰岛素缺陷细胞中选择性丢失。 MafB似乎直接调节这些基因的转录，因为在内源性控制区序列中观察到结合。这些结果表明，MafB通过调节发育过程中产生成熟α和β细胞所需的关键因子的转录来发挥以前未曾表征的作用。

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