Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of Regenerating Gene (REG) protein in fulminant type 1 diabetes.

Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of Regenerating Gene (REG) protein in fulminant type 1 diabetes.
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DOI:
10.1371/journal.pone.0095110
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Kobayashi T
Kobayashi T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Aida K;Saitoh S;Nishida Y;Yokota S;Ohno S;Mao X;Akiyama D;Tanaka S;Awata T;Shimada A;Oikawa Y;Shimura H;Furuya F;Takizawa S;Ichijo M;Ichijo S;Itakura J;Fujii H;Hashiguchi A;Takasawa S;Endo T;Kobayashi T

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胰岛内分泌细胞的支持结构,包括胰岛包裹基底膜(BMS)、细胞外基质(ECM)和可能的细胞团,目前尚不清楚。在非糖尿病状态和人类暴发性1型糖尿病的炎症环境中,研究了胰岛细胞团周围的结构,包括骨髓基质、细胞外基质和胰腺腺泡样细胞团。免疫组织化学和电子显微镜分析表明,人胰岛细胞团和腺泡样细胞团直接粘连在一起,两者之间有桥粒结构和包被的坑状结构。这两个细胞团被包裹在由普通的BMS/ECM组成的连续的包膜中。腺泡样细胞团含有含有再生(REG)Iα蛋白的小泡。含有Reg Iα蛋白的囊泡直接分泌到胰岛细胞。在暴发型1型糖尿病的炎症环境中,腺泡样细胞团过度表达REG Iα蛋白。胰岛内分泌细胞,包括β细胞和非β细胞,被腺泡样细胞团包裹,表现出自我复制,Ki67阳性细胞数量明显增加。与胰岛内分泌细胞接触的腺泡样细胞团明显,因为细胞团被胰岛簇团包裹,并被普通的BMS/ECM包围。此外,腺泡样细胞团表达Reg Iα蛋白,并直接分泌到邻近的非糖尿病状态的胰岛内分泌细胞;在暴发型1型糖尿病炎症环境中,腺泡样细胞团过度表达Reg Iα,胰岛细胞明显自我复制。
Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG) Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.
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DOI: 10.1007/978-90-481-3271-3_10
发表时间: 2010-01-01
期刊: ISLETS OF LANGERHANS
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