Enhanced Expression of miR-199b-5p Promotes Proliferation of Pancreatic β-Cells by Down-Regulation of MLK3
| Autor: | Shingo Nakamura, Nobuyo Yoshida, Hirokazu Matsumoto, Hidefumi Uchiyama, Rie Sato-Kunisada |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Down-Regulation Biology Real-Time Polymerase Chain Reaction Diabetes mellitus genetics Downregulation and upregulation RNA interference Insulin-Secreting Cells microRNA Cyclin E medicine Diabetes Mellitus Animals Orthopedics and Sports Medicine Cyclin D1 RNA Small Interfering Rats Wistar Cells Cultured Cell Proliferation geography geography.geographical_feature_category General Medicine Transfection Oligonucleotides Antisense Islet MAP Kinase Kinase Kinases Molecular biology Rats MicroRNAs medicine.anatomical_structure Gene Expression Regulation Cell culture Emergency Medicine Cancer research RNA Interference Pancreas |
| Zdroj: | MicroRNA (Shariqah, United Arab Emirates). 5(1) |
| ISSN: | 2211-5374 |
| Popis: | Background: The initiation of β-cell proliferation to recover reduced β -cell mass is considered as one of the attractive therapeutic approaches for type 1 and 2 diabetes. In this study, we investigated the involvement of miRNAs in β-cell proliferation. Methods: Global miRNA array analysis of pancreas tissue was carried out using a 60% partial pancreatectomy (PPx) rodent model, which is a well-characterized model for pancreatic regeneration with accelerated proliferation of β -cells. To explore miRNAs with mitogenic activity on β-cells, precursors and antisense oligonucleotides (ASOs) for miRNAs were transfected into a primary islet monolayer cell cultures isolated from adult rats in order to modify their expression and proliferation of β -cells. Results: We found that miR-199b-5p, which was up-regulated 2.6 times in the pancreas of the PPx treated group, significantly enhanced the proliferation of β-cells when its precursor was over-expressed. Target genes of miR-199b-5p were investigated and Mixed lineage kinase-3 (MLK3) was identified as one of the candidates since its expression was down-regulated through an interaction with miR-199b-5p and siRNA treatment for MLK3 enhanced the proliferation of β-cells. Conclusion: Our data suggest that the up-regulation of miR-199b-5p enhances proliferation of β-cells at least in part through down-regulation of MLK3. |
| Databáze: | OpenAIRE |
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