title: MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation.
abstract: 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.
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Sohei
authors.initials: S
authors.lastname: Tsukita
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan; Centre for Metabolic Diseases, Tohoku University Graduate School of Medicine, Japan. Electronic address: yamatetsu-tky@umin.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Munakata
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hosaka
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan; Tohoku University Frontier Research Institute for Interdisciplinary Science, Miyagi, Japan.
authors.forename: Junhong
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shirai
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Kodama
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Asai
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugisawa
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Uno
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Shojiro
authors.initials: S
authors.lastname: Sawada
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Junta
authors.initials: J
authors.lastname: Imai
authors.affiliation: Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan; Centre for Metabolic Diseases, Tohoku University Graduate School of Medicine, Japan; Japan Agency for Medical Research and Development, CREST, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002135:Calcium-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics*; D004195:Disease Models, Animal; D055354:Exosomes; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009687:Nuclear Proteins; D034622:RNA Interference; D012038:Regeneration
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C491605:Cib1 protein, mouse; D056970:Co-Repressor Proteins; C546123:MIRN222 microRNA, mouse; C559899:MLIP protein, mouse; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D009687:Nuclear Proteins
keywords: Cip/Kip family; Diabetes; Exosomes; MicroRNAs; β-cell regeneration