Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

• Matsuki Motoki

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Kabara Maki

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Saito Yukihiro

  Department of Vascular Surgery, Asahikawa Medical University

• Shimamura Kohei

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Minoshima Akiho

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Nishimura Masato

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Aonuma Tatsuya

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University

• Takehara Naofumi

  Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University

• Hasebe Naoyuki

  Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University

• Kawabe Jun-ichi

  Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University

抄録

Background:Capillary pericytes (cPCs), the mural cells of microvessels, play an important role in the formation and maintenance of microvessels; however, little is known about the mechanisms of how cPCs regulate angiogenesis. To identify factors that modulate cPC function, genes whose levels were altered in cPCs during neovessel formation were identified through a microarray screen.Methods and Results:Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary cells including endothelial cells (cECs) and was expressed at a higher level in cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes sprouting from the aorta was increased. Small interfering RNA-mediated downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects, whereas overexpression of Ninj1 attenuated their effects. The production of angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced by the downregulation of Ninj1, and reduced by the overexpression of Ninj1.Conclusions:Ninj1 is a novel regulator for the angiogenic effect of PCs. Specifically, Ninj1 negatively regulates the formation of neovessels, that is, the EC-tube, by reducing the trophic effects of cPCs. (Circ J 2015; 79: 1363–1371)

収録刊行物

• Circulation Journal

  Circulation Journal 79 (6), 1363-1371, 2015

  一般社団法人 日本循環器学会

キーワード

• Angiogenesis
• Endothelial cells
• Ninjurin1
• Pericytes

詳細情報

• CRID: 1390282680082991616
• NII論文ID: 130005073159
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-14-1376
• ISSN: 13474820
• ISSN: 13469843
• NDL書誌ID: 026398920
• PubMed: 25766274
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026398920
• Web Site: https://www.jstage.jst.go.jp/article/circj/79/6/79_CJ-14-1376/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015333550
• 本文言語コード: en
• データソース種別:
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  • Crossref
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