EBioMedicine (2017-02-01)

MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation

  • Sohei Tsukita,
  • Tetsuya Yamada,
  • Kei Takahashi,
  • Yuichiro Munakata,
  • Shinichiro Hosaka,
  • Hironobu Takahashi,
  • Junhong Gao,
  • Yuta Shirai,
  • Shinjiro Kodama,
  • Yoichiro Asai,
  • Takashi Sugisawa,
  • Yumiko Chiba,
  • Keizo Kaneko,
  • Kenji Uno,
  • Shojiro Sawada,
  • Junta Imai,
  • Hideki Katagiri

DOI
https://doi.org/10.1016/j.ebiom.2016.12.002
Journal volume & issue
Vol. 15, no. C
pp. 163 – 172

Abstract

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Major symptoms of diabetes mellitus manifest, once pancreatic β-cell numbers have become inadequate. Although natural regeneration of β-cells after injury is very limited, bone marrow (BM) transplantation (BMT) promotes their regeneration through undetermined mechanism(s) involving inter-cellular (BM cell-to-β-cell) crosstalk. We found that two microRNAs (miRNAs) contribute to BMT-induced β-cell regeneration. Screening murine miRNAs in serum exosomes after BMT revealed 42 miRNAs to be increased. Two of these miRNAs (miR-106b-5p and miR-222-3p) were shown to be secreted by BM cells and increased in pancreatic islet cells after BMT. Treatment with the corresponding anti-miRNAs inhibited BMT-induced β-cell regeneration. Furthermore, intravenous administration of the corresponding miRNA mimics promoted post-injury β-cell proliferation through Cip/Kip family down-regulation, thereby ameliorating hyperglycemia in mice with insulin-deficient diabetes. Thus, these identified miRNAs may lead to the development of therapeutic strategies for diabetes.

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