MafA is required for postnatal proliferation of pancreatic β-cells.
MafA is required for postnatal proliferation of pancreatic β-cells.
复制标题
DOI：
10.1371/journal.pone.0104184
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yasuda K
中科院分区：
文献类型：
--
作者：
Eto K;Nishimura W;Oishi H;Udagawa H;Kawaguchi M;Hiramoto M;Fujiwara T;Takahashi S;Yasuda K
出生后分泌胰岛素的胰腺β细胞的增殖和成熟对于成年人的葡萄糖代谢和疾病发展至关重要。阐明这些事件背后的分子机制将有助于指导干细胞分化为功能性β细胞。β细胞的成熟伴随着MafA（一种胰岛素基因转录因子）表达的增加。MafA敲除胰岛的转录组分析显示MafA是β细胞功能关键的几种分子表达所必需的，包括Glut2、ZnT8、颗粒蛋白、Vdr、Pcsk 1和尿皮质素3，以及催乳素受体（Prlr）及其下游靶细胞周期蛋白D2（Ccnd2）。在小鼠胰岛或β细胞系中抑制MafA表达导致Prlr和Ccnd2的表达减少，并且MafA反式激活Prlr启动子。通过催乳素刺激β细胞导致Stat5B的磷酸化和易位，以及通过Prlr和Jak2增加Ccnd2的核库。与这些结果一致，MafA的缺失导致4周龄时β细胞增殖受损。这些结果表明MafA通过催乳素信号调节出生后β细胞的增殖。
The postnatal proliferation and maturation of insulin-secreting pancreatic β-cells are critical for glucose metabolism and disease development in adults. Elucidation of the molecular mechanisms underlying these events will be beneficial to direct the differentiation of stem cells into functional β-cells. Maturation of β-cells is accompanied by increased expression of MafA, an insulin gene transcription factor. Transcriptome analysis of MafA knockout islets revealed MafA is required for the expression of several molecules critical for β-cell function, including Glut2, ZnT8, Granuphilin, Vdr, Pcsk1 and Urocortin 3, as well as Prolactin receptor (Prlr) and its downstream target Cyclin D2 (Ccnd2). Inhibition of MafA expression in mouse islets or β-cell lines resulted in reduced expression of Prlr and Ccnd2, and MafA transactivated the Prlr promoter. Stimulation of β-cells by prolactin resulted in the phosphorylation and translocation of Stat5B and an increased nuclear pool of Ccnd2 via Prlr and Jak2. Consistent with these results, the loss of MafA resulted in impaired proliferation of β-cells at 4 weeks of age. These results suggest that MafA regulates the postnatal proliferation of β-cells via prolactin signaling.
登录
查看更多内容
影响因子：
--
作者：
Friedrichsen, BN;Richter, HE;Moldrup, A
通讯作者：
Moldrup, A
影响因子：
7.7
作者：
Meier, Juris J.;Butler, Alexandra E.;Butler, Peter C.
通讯作者：
Butler, Peter C.
影响因子：
7.7
作者：
Hang Y;Yamamoto T;Benninger RK;Brissova M;Guo M;Bush W;Piston DW;Powers AC;Magnuson M;Thurmond DC;Stein R
通讯作者：
Stein R
影响因子：
4.8
作者：
Hughes, Elizabeth;Huang, Carol
通讯作者：
Huang, Carol
影响因子：
5.8
作者：
Maccario, M;Grottoli, S;Ghigo, E
通讯作者：
Ghigo, E