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

EBioMedicine

Kenji Uno¹  Hironobu Takahashi¹  Kei Takahashi¹  Junhong Gao¹  Yuta Shirai¹  Yoichiro Asai¹  Yuichiro Munakata¹  Shojiro Sawada¹  Yumiko Chiba¹  Shinichiro Hosaka¹  Tetsuya Yamada¹  Shinjiro Kodama¹  Sohei Tsukita¹  Junta Imai¹  Takashi Sugisawa¹  Keizo Kaneko¹  Hideki Katagiri¹ 

[1] Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan;

关键词: β-cell regeneration;    Diabetes;    MicroRNAs;    Exosomes;    Cip/Kip family;   

DOI  :  10.1016/j.ebiom.2016.12.002

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown