Enhanced Expression of the Key Mitosis Regulator Cyclin B1 Is Mediated by PDZ-Binding Kinase in Islets of Pregnant Mice.
Enhanced Expression of the Key Mitosis Regulator Cyclin B1 Is Mediated by PDZ-Binding Kinase in Islets of Pregnant Mice.
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DOI：
10.1210/js.2017-00338
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发表时间：
2018-03-01
影响因子：
4.1
通讯作者：
Watada H
中科院分区：
文献类型：
--
作者：
Uesato T;Ogihara T;Hara A;Iida H;Miyatsuka T;Fujitani Y;Takeda S;Watada H
胰腺β细胞的增殖被增强以使β细胞质量增加并补偿妊娠期间的胰岛素抵抗。为了阐明所涉及的机制，我们以前研究了从怀孕和非怀孕小鼠的胰岛基因表达谱，发现突触后密度-95/椎间盘大/闭锁小带-1（PDZ）-结合激酶（Pbk），有丝分裂原活化蛋白激酶激酶家族的成员，表达增加，在怀孕小鼠胰岛与对照小鼠胰岛。在妊娠激素中，雌二醇治疗上调Pbk表达。使用小干扰RNA抑制Pbk的表达减少溴脱氧尿苷掺入小鼠胰岛素瘤6细胞，这是伴随着Ccnb 1，参与有丝分裂的调控基因的表达减少。ccnb 1在妊娠期小鼠胰岛中的表达增强。使用腺病毒系统在分离的小鼠胰岛中强制表达Pbk增加了Ccnb 1的表达，并且Pbk抑制剂HI-TOPK-032抑制了从妊娠小鼠分离的胰岛中的Ccnb 1表达。我们的研究结果表明，Pbk有助于在妊娠期间胰岛的扩张，Ccnb 1可能有助于Pbk在β细胞增殖中的作用。PDZ结合激酶在妊娠小鼠胰岛中增加。Pbk表达的抑制降低了MIN 6细胞中BrdU的掺入，这伴随着Ccnb 1表达的降低。
The proliferation of pancreatic β cells is enhanced to enable an increase in β-cell mass and to compensate for insulin resistance during pregnancy. To elucidate the mechanisms involved, we previously investigated islets from pregnant and nonpregnant mice by gene expression profiling and found that the expression of postsynaptic density-95/Discs large/zonula occludens-1 (PDZ)–binding kinase (Pbk), a member of the mitogen-activated protein kinase kinase family, is increased in pregnant mouse islets compared with control mouse islets. Among the pregnancy hormones, treatment with estradiol upregulated Pbk expression. Inhibition of Pbk expression using a small interfering RNA for Pbk reduced bromodeoxyuridine incorporation in mouse insulinoma 6 cells, which was accompanied by a decreased expression of Ccnb1, a regulatory gene involved in mitosis. Ccnb1 expression was augmented in mouse islets during pregnancy. The forced expression of Pbk using an adenovirus system in isolated mouse islets increased Ccnb1 expression, and the Pbk inhibitor HI-TOPK-032 suppressed Ccnb1 expression in islets isolated from pregnant mice. Our results suggest that Pbk contributes to the expansion of islets during pregnancy and that Ccnb1 may assist Pbk in its role in β-cell proliferation. PDZ-binding kinase is increased in islets of pregnant mice. Inhibition of Pbk expression reduces BrdU incorporation in MIN6 cells, which was accompanied by a decreased expression of Ccnb1.