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

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• 作者：Sohei Tsukita^a ; Tetsuya Yamada^a ; ^b ; ^{yamatetsu-tky@umin.ac.jp} ; Kei Takahashi^a ; Yuichiro Munakata^a ; Shinichiro Hosaka^a ; Hironobu Takahashi^a ; Junhong Gao^a ; ^c ; Yuta Shirai^a ; Shinjiro Kodama^a ; Yoichiro Asai^a ; Takashi Sugisawa^a ; Yumiko Chiba^a ; Keizo Kaneko^a ; Kenji Uno^a ; Shojiro Sawada^a ; Junta Imai^a ; Hideki Katagiri^a ; ^b ; ^d
• 关键词：BM ; bone marrow ; BMT ; bone marrow transplantation ; CHOP ; C/EBP homologous protein ; Cip/Kip ; CDK interacting protein/kinase inhibitory protein ; DAPI ; 4&prime ; 6-Diamidino-2-phenylindole ; GFP ; green fluorescent protein ; GNZ ; a nuclear-localized GFP/LacZ fusion protein ; miRNAs ; microRNAs ; PBS ; phosphate-buffered saline ; Pri-miR ; primary microRNA ; STZ ; streptozotocin ; TM ; tamoxifen ; TUNEL ; Terminal deoxynucleotidyl transferase dUTP nick end labeling
• 刊名：EBioMedicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：15
• 期：Complete
• 页码：163-172
• 全文大小：1251 K
• 卷排序：15

文摘

BMT regenerates β-cells in mice with STZ-induced diabetes and increases miR-106b and miR-222 in serum exosomes and islets. Inhibition with anti-miRs against these miRs suppresses BMT-induced β-cell regeneration. Injection of miR-106b and miR-222 mimics promotes β-cell proliferation and improves hyperglycemia in STZ-treated mice.Regeneration of pancreatic β-cells is a promising therapeutic strategy not only for type 1 diabetes but also for certain forms of type 2 diabetes. However, natural regeneration of β-cells hardly ever occurs. Interestingly, bone marrow transplantation (BMT) has been shown to promote β-cell regeneration through an undetermined mechanism(s). In this study, we found that two microRNAs (miR-106b/-222) contribute to BMT-induced β-cell proliferation. Inhibition of miR-106b/-222 using specific anti-miRNAs significantly suppressed BMT-induced β-cell proliferation. Furthermore, intravenously administered miR-106b/222 promoted β-cell proliferation, thereby ameliorating hyperglycemia in mice with insulin-deficient diabetes. Thus, these identified miRNAs may lead to novel therapeutic strategies for diabetes.