Differential expression of cell-cycle regulators in human beta-cells derived from insulinoma tissue.
Differential expression of cell-cycle regulators in human beta-cells derived from insulinoma tissue.
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DOI：
10.1016/j.metabol.2016.02.007
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
S. Ueberberg;A. Tannapfel;P. Schenker;R. Viebahn;W. Uhl;S. Schneider;J. Meier
中科院分区：
文献类型：
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作者：
S. Ueberberg;A. Tannapfel;P. Schenker;R. Viebahn;W. Uhl;S. Schneider;J. Meier
成人胰腺中β细胞复制的低频率限制了β细胞的再生。更好地了解人类β细胞增殖的调控对于制定旨在提高β细胞质量的治疗策略至关重要。方法为了确定控制β细胞增殖的因素，研究了人类胰岛素瘤细胞周期调节作为β细胞增殖增加的模型（n = 11）和良性胰腺肿瘤患者健康胰腺组织（n = 9）。组织切片共染色，检测胰岛素和细胞周期蛋白。在进行激光捕获显微解剖后，通过qRT-PCR确定β细胞中选定的细胞周期因子的转录水平。结果胰岛素瘤组β细胞复制频率为3.74±0.92%，对照组为0.11±0.04% （p = 0.0016）。胰岛素瘤组织中p21表达较高（p = 0.0058）， Rb表达较高（p = 0.085），而p16 （p < 0.0001）、Cyclin C （p < 0.0001）、p57 （p = 0.018）表达较低。Cyclin D3丰度（p = 0.62）和p27丰度（p = 0.68）各组间无显著差异。qRT-PCR证实胰岛素瘤中p16 （p < 0.0001）和p57 （p = 0.012）表达降低，Cyclin D3 （p = 0.77）和p27 （p = 0.55）表达不变。结论胰岛素瘤β细胞与健康成人β细胞中某些细胞周期因子的表达存在显著差异。靶向这种差异调节的细胞周期蛋白可能会成为未来增强β细胞再生的策略。
IntroductionThe low frequency of beta-cell replication in the adult human pancreas limits beta-cell regeneration. A better understanding of the regulation of human beta-cell proliferation is crucial to develop therapeutic strategies aiming to enhance beta-cell mass.MethodsTo identify factors that control beta-cell proliferation, cell-cycle regulation was examined in human insulinomas as a model of increased beta-cell proliferation (n = 11) and healthy pancreatic tissue from patients with benign pancreatic tumors (n = 9). Tissue sections were co-stained for insulin and cell-cycle proteins. Transcript levels of selected cell-cycle factors in beta-cells were determined by qRT-PCR after performing laser-capture microdissection.ResultsThe frequency of beta-cell replication was 3.74 ± 0.92% in the insulinomas and 0.11 ± 0.04% in controls (p = 0.0016). p21 expression was higher in insulinomas (p = 0.0058), and Rb expression was higher by trend (p = 0.085), whereas p16 (p < 0.0001), Cyclin C (p < 0.0001), and p57 (p = 0.018) expression levels were lower. The abundance of Cyclin D3 (p = 0.62) and p27 (p = 0.68) was not different between the groups. The reduced expression of p16 (p < 0.0001) and p57 (p = 0.012) in insulinomas and the unchanged expression of Cyclin D3 (p = 0.77) and p27 (p = 0.55) were confirmed using qRT-PCR.ConclusionsThe expression of certain cell-cycle factors in beta-cells derived from insulinomas and healthy adults differs markedly. Targeting such differentially regulated cell-cycle proteins may evolve as a future strategy to enhance beta-cell regeneration.