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

Kaoru Aida, Sei Saitoh, Yoriko Nishida, Sadanori Yokota, Shinichi Ohno, Xiayang Mao, Daiichiro Akiyama, Shoichiro Tanaka, Takuya Awata, Akira Shimada, Youichi Oikawa, Hiroki Shimura, Fumihiko Furuya, Soichi Takizawa, Masashi Ichijo, Sayaka Ichijo, Jun Itakura, Hideki Fujii, Akinori Hashiguchi, Shin TakasawaToyoshi Endo, Tetsuro Kobayashi

研究成果: Article

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Background: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. Procedures: 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. Result: 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) Ia protein. The vesicles containing REG Ia protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Ia 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. Conclusion: 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 Ia protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Ia in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.

元の言語English
記事番号e95110
ジャーナルPloS one
9
発行部数4
DOI
出版物ステータスPublished - 2014 4 23

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    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., ... Kobayashi, T. (2014). 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. PloS one, 9(4), [e95110]. https://doi.org/10.1371/journal.pone.0095110