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.

piRNA‐19128 regulates spermatogenesis by silencing of KIT in chicken

“…Next, we used miRanda to identify the target genes of these piRNAs and identified 630 genes. GO enrichment analysis identified five genes, namely, acyl‐CoA oxidase 1 ( ACOX1 ), V‐kit Hardy‐Zuckerman 4 feline sarcoma viral oncogene homolog, Fc fragment of IgG‐binding protein ( FCGBP ), androgen receptor ( AR ), and receptor tyrosine kinase‐like orphan receptor 2 ( ROR2 ) (Figure A). WEGO analysis indicated that these five genes played different roles in spermatogenesis.…”

“…Spermatogenesis is a complex process involving mitosis and meiosis. Sperm formation depends on the expression and regulation of several genes such as KIT at different stages . KIT is an important gene in germline stem cells.…”

“…Next, we used miRanda to identify the target genes of these piRNAs and identified 630 genes. GO enrichment analysis identified five genes, namely, acyl-CoA oxidase 1 (ACOX1), V-kit Hardy-Zuckerman 4 feline sarcoma viral PGCs 30851348 19850783 64 1864758 903798 48 PGC-RIP 47612284 22773341 48 1680562 177945 11 SSCs 31461002 20074827 64 1654396 701020 42 SSC-RIP 42719348 20672273 48 1130054 52828 5 Sa 46273957 19022593 41 8650846 4577172 53 Sperm 29792129 7644401 26 3362195 1170860 35 Sperm-RIP 46886993 27219660 58 505839 14392 3 oncogene homolog, 25 Fc fragment of IgG-binding protein (FCGBP), androgen receptor (AR), and receptor tyrosine kinase-like orphan receptor 2 (ROR2) ( Figure 6A). WEGO analysis indicated that these five genes played different roles in spermatogenesis.…”

“…KIT is involved in cytokine-cytokine receptor interaction, organism-specific biosystem formation, and melanogenesis. 25 Moreover, it plays an important regulatory role in gonadal development. Our results suggest a negative correlation between piRNA-19128 and KIT expression ( Figures 7A and 7B).…”

Exosomes and diabetes

“…Importantly, intravenous administration of artificial miR‐106b‐5p and miR‐222‐3p mimics associated with atelocollagen as a carrier also promoted post‐injury β‐cell proliferation. The therapeutic miRNAs targeted and downregulated the cyclin dependent kinase (CDK) interacting protein/kinase inhibitory protein (CIP/KIP) family of cell cycle repressors, resulting in increased β‐cell mass and a better control of glycaemia (Table ). These data suggest that extracellular delivery of miRNAs mediated by inert carrier molecules is an alternative strategy to the use of the exosomes themselves.…”