The Third Medical Clinic, Justus Liebig University, Germany.
Islets. 2009 Jul-Aug;1(1):19-25. doi: 10.4161/isl.1.1.8530.
Insulin producing β-cells are exposed to hypoxic stress in the early period after islet transplantation. Although it has been suggested that hypoxia leads to islet loss, the underlying mechanisms are unclear. In this study, the early transcriptional profiles of b cell response to hypoxia were determined by using the Affymetrix Murine Genome Array U74Av2 GeneChip (about 12,422 genes). In addition to the upregulation of genes associated with glycolysis, genes related to apoptosis and stress response were also upregulated. The downregulated genes on hypoxia are classified as transcription and inflammatory response. These findings were confirmed by TUNEL assay and real-time reverse transcription-PCR for mRNA of genes related to apoptosis. On the other hand, we have found that the transcription factor NFκB was activated by hypoxia in islet cells. The affected genes involved in the activated NFκB pathway were mainly categorized as apoptosis-related genes by quantitative real-time PCR array (84 genes). Our comprehensive analysis of transcriptional changes of islets by hypoxia may assist the development of strategies that protect islet grafts from early loss.
胰岛移植后早期，产生胰岛素的β细胞会受到缺氧应激。虽然有人提出缺氧会导致胰岛损失，但潜在机制尚不清楚。本研究采用 Affymetrix Murine Genome Array U74Av2 GeneChip（约 12422 个基因）检测了β细胞对缺氧早期反应的转录谱。除了与糖酵解相关的基因上调外，与凋亡和应激反应相关的基因也上调。缺氧下调的基因被归类为转录和炎症反应。这些发现通过 TUNEL 检测和实时逆转录-PCR 对与凋亡相关基因的 mRNA 得到了证实。另一方面，我们发现 NFκB 转录因子在胰岛细胞中被缺氧激活。通过定量实时 PCR 阵列分析，受激活 NFκB 通路影响的基因主要归类为凋亡相关基因（84 个基因）。我们对缺氧诱导的胰岛转录变化的综合分析可能有助于开发保护胰岛移植物免受早期损失的策略。
