| First Author | Eto K | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 8 | Pages | e104184 |
| PubMed ID | 25126749 | Mgi Jnum | J:218982 |
| Mgi Id | MGI:5619218 | Doi | 10.1371/journal.pone.0104184 |
| Citation | Eto K, et al. (2014) MafA is required for postnatal proliferation of pancreatic beta-cells. PLoS One 9(8):e104184 |
| abstractText | The postnatal proliferation and maturation of insulin-secreting pancreatic beta-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 beta-cells. Maturation of beta-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 beta-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 beta-cell lines resulted in reduced expression of Prlr and Ccnd2, and MafA transactivated the Prlr promoter. Stimulation of beta-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 beta-cells at 4 weeks of age. These results suggest that MafA regulates the postnatal proliferation of beta-cells via prolactin signaling. |
