MafA is required for postnatal proliferation of pancreatic β-cells

Koki Eto, Wataru Nishimura, Hisashi Oishi, Haruhide Udagawa, Miho Kawaguchi, Masaki Hiramoto, Toshiyoshi Fujiwara, Satoru Takahashi, Kazuki Yasuda

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numbere104184
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 15 2014

Fingerprint

Prolactin Receptors
Cyclin D2
Cell Proliferation
cyclins
Prolactin
prolactin
Urocortins
cells
Insulin
cell proliferation
insulin
Phosphorylation
Insulin-Secreting Cells
Gene Expression Profiling
Stem cells
Islets of Langerhans
Metabolism
adult development
transcriptomics
Transcription Factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Eto, K., Nishimura, W., Oishi, H., Udagawa, H., Kawaguchi, M., Hiramoto, M., ... Yasuda, K. (2014). MafA is required for postnatal proliferation of pancreatic β-cells. PLoS One, 9(8), [e104184]. https://doi.org/10.1371/journal.pone.0104184

MafA is required for postnatal proliferation of pancreatic β-cells. / Eto, Koki; Nishimura, Wataru; Oishi, Hisashi; Udagawa, Haruhide; Kawaguchi, Miho; Hiramoto, Masaki; Fujiwara, Toshiyoshi; Takahashi, Satoru; Yasuda, Kazuki.

In: PLoS One, Vol. 9, No. 8, e104184, 15.08.2014.

Research output: Contribution to journalArticle

Eto, K, Nishimura, W, Oishi, H, Udagawa, H, Kawaguchi, M, Hiramoto, M, Fujiwara, T, Takahashi, S & Yasuda, K 2014, 'MafA is required for postnatal proliferation of pancreatic β-cells', PLoS One, vol. 9, no. 8, e104184. https://doi.org/10.1371/journal.pone.0104184
Eto K, Nishimura W, Oishi H, Udagawa H, Kawaguchi M, Hiramoto M et al. MafA is required for postnatal proliferation of pancreatic β-cells. PLoS One. 2014 Aug 15;9(8). e104184. https://doi.org/10.1371/journal.pone.0104184
Eto, Koki ; Nishimura, Wataru ; Oishi, Hisashi ; Udagawa, Haruhide ; Kawaguchi, Miho ; Hiramoto, Masaki ; Fujiwara, Toshiyoshi ; Takahashi, Satoru ; Yasuda, Kazuki. / MafA is required for postnatal proliferation of pancreatic β-cells. In: PLoS One. 2014 ; Vol. 9, No. 8.
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