MafA is required for postnatal proliferation of pancreatic β-cells
| Autor: | Satoru Takahashi, Masaki Hiramoto, Wataru Nishimura, Kazuki Yasuda, Miho Kawaguchi, Hisashi Oishi, Koki Eto, Toshiyoshi Fujiwara, Haruhide Udagawa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Maf Transcription Factors Large Physiology Organogenesis Developmental Signaling Gene Expression lcsh:Medicine Calcitriol receptor Transcriptome Signaling Molecules Mice Endocrinology Cell Signaling Endocrine Signaling Genes Reporter Insulin-Secreting Cells Morphogenesis Medicine and Health Sciences Cyclin D2 Promoter Regions Genetic lcsh:Science Regulation of gene expression Mice Knockout Multidisciplinary Pancreas Development Signal transduction Research Article Signal Transduction medicine.medical_specialty endocrine system Receptors Prolactin Biology Cell Line Islets of Langerhans Internal medicine medicine Diabetes Mellitus Animals Humans Transcription factor Cell Proliferation Growth Control Diabetic Endocrinology Endocrine Physiology Prolactin receptor Gene Expression Profiling lcsh:R Biology and Life Sciences Cell Biology Rats Insulin receptor Animals Newborn Gene Expression Regulation Metabolic Disorders Hyperglycemia biology.protein lcsh:Q Transcriptional Signaling Organism Development Developmental Biology |
| Zdroj: | PLoS ONE, Vol 9, Iss 8, p e104184 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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