Enhanced nerve-mast cell interaction mediated by cell adhesion molecule 1 in stress-related diseases

• Project/Area Number: 24590492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kinki University
• Principal Investigator: ITO Akihiko 近畿大学, 医学部, 教授 (80273647)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 接着分子 / 神経‐免疫相互作用 / アトピー性皮膚炎 / 脱顆粒 / 細胞間接着力 / 接着力 / 神経免疫学 / ストレス応答 / 神経－マスト細胞相互作用 / 過敏性腸症候群 / フェムト秒レーザー / 神経源性炎症

Outline of Final Research Achievements

Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly through enhanced sensory nerve-skin mast cell interaction. Cell adhesion molecule 1 (CADM1) is known to mediate nerve-mast cell interaction. In a hapten-induce AD mouse model, AD-like lesional mast cells expressed three-fold more CADM1 transcripts than non-lesional mast cells. In nerve-mast cell coculture, CADM1 overexpression in IC2 mast cells strengthened dorsal root ganglion neurite-IC2 cell adhesion and doubled the population of IC2 cells responding to nerve activation. Increased expression of CADM1 in mast cells appeared to be a cause of enhanced sensory nerve-mast cell interaction in a hapten-induced AD mouse model, and might be involved in stress-induced deterioration of human AD.

Research Products

• [Journal Article] Increased ectodomain shedding of lung-epithelial cell adhesion molecule 1 as a cause of increased alveolar cell apoptosis in emphysema. (2014)
  • Author(s): Mimae T, et al
  • Journal Title: Thorax Volume: 69 Issue: 3 Pages: 223-231
  • DOI: 10.1136/thoraxjnl-2013-203867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased ectodomain shedding of cell adhesion molecule 1 from pancreatic islets in type 2 diabetic pancreata: correlation with hemoglobin A1c levels. (2014)
  • Author(s): Inoue T, et al
  • Journal Title: Plos One Volume: 9 Issue: 6 Pages: 00-00
  • DOI: 10.1371/journal.pone.0100988
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gefitinib and luteolin cause growth arrest of human prostate cancer PC-3 cells via inhibition of Cyclin G-associated kinase and induction of miR-630 (2014)
  • Author(s): Sakurai MA, Ozaki Y, Okuzaki D, Naito Y, Sasakura T, Okamoto A, Tabara H, Inoue T, Hagiyama M, Ito A, Yabuta N, and Nojima H.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e100124-e100124
  • DOI: 10.1371/journal.pone.0100124
  • Peer Reviewed / Open Access
• [Journal Article] α- Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma. (2014)
  • Author(s): Ito M, Hagiyama M, Mimae T, Inoue T, Kato T, Yoneshige A, Nakanishi J, Kondo T, Okada M, Ito A.
  • Journal Title: Breast Cancer Res Treat Volume: 144 Issue: 1 Pages: 59-69
  • DOI: 10.1007/s10549-014-2859-0
  • Peer Reviewed / Open Access
• [Journal Article] A novel approach to pseudopodia proteomics: excimer laser etching, two-dimensional difference gel electrophoresis, and confocal imaging. (2014)
  • Author(s): Mimae T, et al
  • Journal Title: Protocol Exchange Volume: -
  • DOI: 10.1038/protex.2014.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A decrease in glomerular endothelial cells and endothelial-mesenchymal transition during glomerulosclerosis in the Tensin2-deficient mice (ICGN strain). (2014)
  • Author(s): Kato T, et al
  • Journal Title: Acta Histochem Cytochem Volume: 47 Pages: 265-271
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer. (2014)
  • Author(s): Togashi Y, et al
  • Journal Title: Mol Cancer Volume: 13 Pages: 126-126
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. (2014)
  • Author(s): Hayashi H, Arao T, Togashi Y, Kato H, Fujita Y, De Velasco MA, Kimura H, Matsumoto K, Tanaka K, Okamoto I, Ito A, Yamada Y, Nakagawa K, Nishio K.
  • Journal Title: Oncogene Volume: in press
  • Peer Reviewed
• [Journal Article] The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. (2013)
  • Author(s): Hayashi, H., Arao, T., Togashi, Y., Kato, H., Velasco, MA., Kimura, H., Matsumoto, K., Tanaka, K., Okamoto, I., Ito, A., Yamada, Y., Nakagawa, K., Nishio, K.
  • Journal Title: Oncogene Volume: E-pub ahead or print Issue: 2 Pages: 199-208
  • DOI: 10.1038/onc.2013.547
  • Peer Reviewed / Open Access
• [Journal Article] N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability. (2013)
  • Author(s): Yabuta N, Mukai S, Okamoto A, Okuzaki D, Suzuki H, Torigata K, Yoshida K, Okada N, Miura D, Ito A, Ikawa M, Okabe M, Nojima H.
  • Journal Title: Journal of Cell Science Volume: 126 Issue: 2 Pages: 508-520
  • DOI: 10.1242/jcs.113431
  • Peer Reviewed
• [Journal Article] Cell adhesion molecule 1 is a new osteoblastic cell adhesion molecule and a diagnostic marker for osteosarcoma. (2013)
  • Author(s): Inoue T, Hagiyama M, Enoki E, Sakurai MA, Tan A, Wakayama T, Iseki S, Murakami Y, Fukuda K, Hamanishi C, Ito A.
  • Journal Title: Life Sci Volume: 92 Issue: 1 Pages: 91-99
  • DOI: 10.1016/j.lfs.2012.10.021
  • Peer Reviewed
• [Journal Article] Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis (2013)
  • Author(s): Man Hagiyama, Takao Inoue, Tadahide Furuno, Takanori Iino, Saori Itami, Mamoru Nakanishi, H. Asada, Yoichiroh Hosokawa and Akihiko Ito
  • Journal Title: Brit. J. Dermato Volume: (In press) Issue: 4 Pages: 771-778
  • DOI: 10.1111/bjd.12108
  • Peer Reviewed
• [Journal Article] Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve–mast cell interaction in a hapten-induced mouse model of atopic dermatitis. (2013)
  • Author(s): Hagiyama M, et al
  • Journal Title: Brit J Dermatol Volume: 168 Pages: 771-778
  • Peer Reviewed
• [Journal Article] Novel application for pseudopodia proteomics using excimer laser ablation and two-dimensional difference gel electrophoresis. (2012)
  • Author(s): Ito A, et al
  • Journal Title: Lab Invest Volume: 92 Pages: 1347-1385
  • Peer Reviewed
• [Journal Article] Upregulation of notch2 and six1 is associated with progression of early-stage lung adenocarcinoma and a more aggressive phenotype at advanced stages. (2012)
  • Author(s): Mimae T, et al
  • Journal Title: Clin Cancer Res Volume: 18 Pages: 945-955
  • Peer Reviewed
• [Journal Article] communication among pancreatic islet α-cells and prevents their excessive secretion of glucagon. (2012)
  • Author(s): Ito A, et al
  • Journal Title: Islets Volume: 4 Pages: 49-55
  • Peer Reviewed
• [Presentation] Mechanical response of single nerve cells estimated by femtosecond laser-induced impulsive force. (2015)
  • Author(s): Iino T, Furuno T, Hagiyama M, Ito A, Hosokawa Y
  • Organizer: SPIE Photonics West
  • Place of Presentation: San Francisco
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] 三次元培養下での肺腺腫瘍様構造の構築. (2014)
  • Author(s): 加藤貴史, 伊藤彰彦
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] アクチン結合性アダプター蛋白α-parvinは偽足突起構成要素であり、小葉乳癌のリンパ節転移に関与する. (2014)
  • Author(s): 萩山 満, 伊藤彰彦
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 肺気腫の新規発症機序：接着分子CADM１の酵素的切断亢進による肺胞上皮アポトーシスの亢進. (2014)
  • Author(s): 米重あづさ，伊藤彰彦
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島（広島国際会議場）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 複数の剖検従事者への結核菌感染源と推定された上行結腸・直腸多発癌術後の一剖検例. (2014)
  • Author(s): 橋本重夫，伊藤彰彦
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島（広島国際会議場）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 骨芽細胞の新規接着分子CADM1は骨肉腫の診断マーカーとして有用である. (2014)
  • Author(s): 井上敬夫，伊藤彰彦
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島（広島国際会議場）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] マスト細胞における接着分子CADM1の発現上昇：アトピー性皮膚炎のストレス感受性への関与. (2014)
  • Author(s): 萩山満，井上敬夫，米重あづさ，伊藤彰彦.
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
• [Presentation] エキシマレーザーによる癌細胞偽足突起の選択的採取とプロテオミクス (2013)
  • Author(s): 萩山満，伊藤彰彦.
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 分子病態学におけるレーザープロセシング技術応用の最前線. (2013)
  • Author(s): 伊藤彰彦.
  • Organizer: 第74回応用物理学会秋季学術講演会
  • Place of Presentation: 京都
  • Invited
• [Presentation] Femtosecond laser-assisted estimation of time development of cell-cell adhesion force between neurite and mast cell. (2013)
  • Author(s): Takanori Iino, Man Hagiyama, Tadahide Furuno, Akihiko Ito, Yoichiroh Hosokawa.
  • Organizer: Conference on Lasers and Electro-Optics Pacific Rim 2013.
  • Place of Presentation: Kyoto, Japan
• [Presentation] Novel application for pseudopodial proteomics using excimer laser ablation and two-dimensional difference gel electrophoresis. (2013)
  • Author(s): Takahiro Mimae, Akihiko Ito, Man Hagiyama, Tadashi Kondo, Morihito Okada.
  • Organizer: AACR 2013.
  • Place of Presentation: Washington DC, America
• [Remarks] 近畿大学医学部病理学講座
  • URL: http://www.med.kindai.ac.jp/patho/
• [Remarks] 近畿大学医学部病理学講座
  • URL: http://www.med.kindai.ac.jp/patho/
• [Remarks] 近畿大学医学部病理学講座
  • URL: http://www.med.kindai.ac.jp/patho/