Developmentally regulated expression of survivin in human pancreatic islets
Developmentally regulated expression of survivin in human pancreatic islets
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DOI：
10.1007/s10024-003-2014-0
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发表时间：
2003-09-01
影响因子：
1.9
通讯作者：
Gianani, R
中科院分区：
文献类型：
--
作者：
Liggins, C;Orlicky, DJ;Gianani, R
胰岛细胞凋亡在内分泌胰腺的正常发育以及 I 型和 II 型糖尿病的发病机制中发挥作用。在正常和病理情况下调节胰岛细胞死亡和存活的分子机制尚未完全阐明。凋亡蛋白抑制剂（IAP）Survivin 具有通过多种机制介导的抗凋亡功能；其中包括抑制 caspase 3 和 caspase 7。据报道，生存素在人类胎儿胰岛中表达，它可能在胰腺重塑和胰岛稳态中发挥作用。然而，没有关于其在新生儿或成人胰岛中的表达或其在任何特定胰岛细胞亚型中的表达的数据。我们通过免疫组织化学鉴定了 5/5 胎儿胰腺的 α 细胞和 β 胰岛细胞中 Survivin 的表达。相反，胎儿δ细胞未能表现出任何可检测水平的生存素表达。随后，5/5 新生儿和 5/5 成人受试者的 β 细胞中存活蛋白表达丢失，但 α 细胞中并未丢失。新生儿和成人 delta 细胞维持胎儿胰岛中缺乏存活蛋白表达。这些数据表明，不同亚型的胰岛细胞的生存素表达模式不同。此外，β细胞中生存素的表达受到发育调节。
Islet cell apoptosis plays a role in both normal development of the endocrine pancreas and in the pathogenesis of Type I and Type II diabetes. The molecular mechanisms regulating islet cell death and survival in both normal and pathological situations are still not completely elucidated. The inhibitor of apoptosis protein (IAP) Survivin has an anti-apoptotic function mediated by several mechanisms; these include inhibiting caspase 3 and caspase 7. Survivin expression has been reported in human fetal islets and it may play a role in pancreatic remodeling and islet homeostasis. However, there are no data concerning either its expression in neonate or adult islets or its expression in any specific subtype of islet cells. We identified Survivin expression by immunohistochemistry in alpha cells and beta islet cells of 5/5 fetal pancreases. In contrast, fetal delta cells failed to demonstrate any detectable level of Survivin expression. Survivin expression was subsequently lost in the beta cells but not the alpha cells of 5/5 newborns and 5/5 adult subjects. Neonatal and adult delta cells maintained the lack of Survivin expression seen in fetal islets. These data show that different subtypes of islet cells differ in their pattern of Survivin expression. Furthermore, expression of Survivin in the beta cells is developmentally regulated.