The MafA transcription factor becomes essential to islet β-cells soon after birth.
The MafA transcription factor becomes essential to islet β-cells soon after birth.
复制标题
作者：
Hang Y;Yamamoto T;Benninger RK;Brissova M;Guo M;Bush W;Piston DW;Powers AC;Magnuson M;Thurmond DC;Stein R
在啮齿动物胰岛细胞中，大的MAF转录因子MafA和MafB的表达具有不同的时空模式。对MafA−/−和胰腺特异性MafA∆PANC缺失突变小鼠的分析表明，MafA在成人β细胞活性中起主要作用，不同于MafB在胚胎中的重要性。我们在这里的兴趣是准确地定义MafA对β细胞具有重要功能的时间，确定这一点是如何受到出生后短暂的MafB产生的影响的，并确定在这一时期受MafA调控的基因。我们发现，3周龄的Mafa-βPANC小鼠的胰岛细胞组织、β-细胞质量和Mafb-细胞功能受到影响，而在Mafa-ΔPANC；MAFB+/Δ小鼠中，则较早受到影响。全基因组微阵列图谱、电子显微镜和代谢分析的组合被用来揭示Mafa的控制机制。例如，β细胞的复制是通过对周期蛋白D2的调节而产生的，而对颗粒对接的影响则影响了第一时相胰岛素的分泌。此外，胚胎MafB和出生后MafA基因表达调控的基因也存在显著差异。这些结果不仅清楚地解释了为什么MafA是胰岛β细胞的重要转录调节因子，而且也明确了为什么细胞成熟涉及到与MafB的协调作用。
The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial–temporal patterns in rodent islet cells. Analysis of Mafa−/− and pancreas-specific Mafa∆panc deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in MafaΔpanc mice and compromised earlier in MafaΔpanc;Mafb+/− mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB.
登录
查看更多内容
影响因子：
4.8
作者：
Guo, Shuangli;Vanderford, Nathan L.;Stein, Roland
通讯作者：
Stein, Roland
影响因子：
10.9
作者：
Hang, Yan;Stein, Roland
通讯作者：
Stein, Roland
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.
影响因子：
2.7
作者：
Gannon, Maureen;Ables, Elizabeth Tweedie;Wright, Christopher V. E.
通讯作者：
Wright, Christopher V. E.
影响因子：
25
作者：
Blanchi, B;Kelly, LM;Sieweke, MH
通讯作者：
Sieweke, MH