Title:Enhanced Expression of miR-199b-5p Promotes Proliferation of Pancreatic β-Cells by Down-Regulation of MLK3
Volume: 5
Issue: 1
Author(s): Rie Sato-Kunisada, Nobuyo Yoshida, Shingo Nakamura, Hidefumi Uchiyama and Hirokazu Matsumoto
Affiliation:
Keywords:
Diabetes, miR-199b-5p, MLK3, pancreatectomy, pancreatic β-cell, proliferation.
Abstract: 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.
