To understand molecular bases of how intraluminal pressure elevation leads to the development of degenerative lesions

• Project/Area Number: 15K15113
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kindai University
• Principal Investigator: ITO Akihiko 近畿大学, 医学部, 教授 (80273647)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 内圧上昇 / 変性 / 緑内障 / 接着分子 / メカノバイオロジー / メカノパソロジー / two-chamber培養装置 / 病的内圧上昇 / 組織変性 / 細胞変性 / アポトーシス

Outline of Final Research Achievements

Elevation of intraluminal, such as intraocular and intra-renal pelvic, pressure causes neuronal and mucosal degeneration. The threshold is fairly low and constant, approximately 30 cmH2O. A new two-chamber culture system was devised wherein cells were cultured on a semipermeable membrane and subjected to increased medium height (water pressure up to 60 cmH2O). Primary cultured mouse neurons were found to fall into axonal degeneration when loaded with 30 cmH2O or more, in association with increased ectodomain shedding of CADM1, an IgCAM member expressed on neuritic cell membrane. The cell-side remnant produced by shedding appeared to be involved in axonal degeneration. Columnar epithelial cells were flattened and growth suppressed when loaded with 30 cmH2O or more. This work contributes to our understanding the pathophysiology of the development of degenerative lesions caused by low static pressure burden.

Research Products

• [Journal Article] Modest static pressure can cause enteric nerve degeneration through ectodomain shedding of cell adhesion molecule 1. (2016)
  • Author(s): Yoneshige A, Hagiyama M, Inoue T, Tanaka T, Ri A, Ito A
  • Journal Title: Mol Neurobiol Volume: - Issue: 8 Pages: 1-1
  • DOI: 10.1007/s12035-016-0166-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Decreased expression of Met during differentiation in rat lung (2016)
  • Author(s): T Kato, K Oka, T Nakamura, A Ito
  • Journal Title: European Journal of Histochemistry Volume: 60 Issue: 1 Pages: 2575-2575
  • DOI: 10.4081/ejh.2016.2575
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] FGFR gene alterations in lung squamous cell carcinoma are potential targets for the multikinase inhibitor nintedanib. (2016)
  • Author(s): Hibi M, Kaneda H, Tanizaki J, Sakai K, Togashi Y, Terashima M, De Velasco M, Fujita Y, Banno E, Nakamura Y, Takeda M, Ito A, Mitsudomi T, Nakagawa K, Okamoto I, Nishio K
  • Journal Title: Cancer Sci Volume: 107(11) Issue: 11 Pages: 1667-1676
  • DOI: 10.1111/cas.13071
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of femtosecond lasers for application of acupuncture therapy. (2016)
  • Author(s): Ohta M, Hosokawa Y, Hatano N, Sugano A, Ito A, Takaoka Y
  • Journal Title: Lasers in Med Sci Volume: - Issue: 9 Pages: 2167-2171
  • DOI: 10.1007/s10103-016-2124-3
  • NAID: 120006377642
  • Peer Reviewed / Open Access
• [Journal Article] Novel method (OSNA) for the diagnosis of lymph node metastasis in patients with non-small cell lung cancer (NSCLC): Results of a multicenter prospective study. (2016)
  • Author(s): Nakagawa K, Asamura H, Tsuta K, Nagai K, Yamada E, Ishi G, Mitsudomi T, Ito A, Higashiyama M, Tomita Y, Inoue M, Morii E, Matsuura N, Okumura M
  • Journal Title: Lung Cancer Volume: 97 Pages: 1-7
  • DOI: 10.1016/j.lungcan.2016.03.015
  • Peer Reviewed / Open Access
• [Journal Article] Significance of FGF9 gene in resistance to anti-EGFR therapies targeting colorectal cancer: a subset of colorectal cancer patients with FGF9 upregulation may be resistant to anti-EGFR therapies (2016)
  • Author(s): Mizukami T, Togashi Y, Naruki S, Banno E, Terashima M, De Velasco MA, Sakai K, Yoneshige A, Hayashi H, Fujita Y, Tomida S, Nakajima TE, Fujino T, Boku N, Ito A, Nakagawa K, Nishio K.
  • Journal Title: Molecular Carcinogenesis Volume: Epub Issue: 1 Pages: 106-117
  • DOI: 10.1002/mc.22476
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Increased ectodomain shedding of cell adhesion molecule 1 as a cause of type II alveolar epithelial cell apoptosis in patients with idiopathic interstitial pneumonia. (2015)
  • Author(s): Yoneshige A, Hagiyama M, Inoue T, Mimae T, Kato T, Okada M, Enoki E, Ito A
  • Journal Title: Respiratory Research Volume: 16 Pages: 19-19
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The intracellular domain of cell adhesion molecule 1 is present in emphysematous lungs and induces lung epithelial cell apoptosis. (2015)
  • Author(s): 1.Hagiyama, M., Yoneshige, A., Inoue, T., Sato, Y., Mimae, T., Okada, M., Ito, A.
  • Journal Title: J. Biomed. Sci Volume: 22 Issue: 1 Pages: 67-67
  • DOI: 10.1186/s12929-015-0173-8
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic actions of cell adhesion molecule 1 in pulmonary emphysema and atopic dermatitis. (2015)
  • Author(s): Yoneshige A, Hagiyama M, Fujita M, Ito A
  • Journal Title: Front Cell Dev Biol Volume: - Pages: 75-75
  • DOI: 10.3389/fcell.2015.00075
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bronchioalveolar morphogeneis of human bronchial epithelial cells depending upon hepatocyte growth factor. (2015)
  • Author(s): Kato T, Oka K, Nakamura T, Ito A
  • Journal Title: J Cell Mol Med Volume: 19 Issue: 12 Pages: 2818-2826
  • DOI: 10.1111/jcmm.12672
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinoma. (2015)
  • Author(s): Yoshioka Y, Togashi Y, Chikugo T, Kogita A, Terashima M, Mizukami T, Hayashi H, Sakai K, de Velasco MA, Tomida S, Fujita Y, Tokoro T, Ito A, Okuno K, Nishio K
  • Journal Title: Cancer Volume: 121(24) Issue: 24 Pages: 4359-4368
  • DOI: 10.1002/cncr.29676
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] New challenges in pseudopodial proteomics by a laser-assisted cell etching technique. (2015)
  • Author(s): Mimae T, Ito A
  • Journal Title: Biochim Biophys Acta. Volume: 1854 Issue: 6 Pages: 538-546
  • DOI: 10.1016/j.bbapap.2014.10.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 接着分子cell adhesion molecule 1の細胞内断片による肺上皮アポトーシス誘導：肺気腫発症への関与. (2016)
  • Author(s): 萩山満、米重あづさ、井上敬夫、伊藤彰彦
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
• [Presentation] 悪性上皮性腫瘍内の肉腫様成分における骨芽細胞分化マーカーの発現. (2016)
  • Author(s): 米重あづさ、村上哲平、井上敬夫、西村俊司、伊藤彰彦
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
• [Presentation] Heart-bound adiponectin, not serum adiponectin, correlates with cardiac hypertrophy in stroke-prone spontaneously hypertensive rats. (2016)
  • Author(s): Inoue T, Takemori K, Mizuguchi N, Kimura M, Chikugo T, Hagiyama M, Yoneshige A, Mori T, Kometani T, Itoh T, Sato T, Ito A
  • Organizer: The 26th Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Coex (Convention & Exhibition Center) （Seoul, Korea）
  • Int'l Joint Research
• [Presentation] 肺癌に於ける次世代シーケンサーを用いた変異解析に基づく分子標的薬適応決定(Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer) (2016)
  • Author(s): 武田真幸、坂井和子、林秀敏、田中薫、高濱隆幸、吉田健史、岩朝勤、光冨徹哉、伊藤彰彦、西尾和人、中川和彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] マウスモデルを用いた DNA損傷修復機能抑制による治療関連白血病予防効果の検討(Modest attenuation of DNA damage repair delays therapyrelated cancer in mouse model). (2016)
  • Author(s): 岡田斉、T Kit、太田一成、古室暁義、A Koch、伊藤彰彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 癌による内腔狭窄に伴って拡張した大腸における腸管神経変性： CADM1/TSLC1の関与(Enteric nerve degeneration in the colon dilated due to the luminal stenosis by cancer: involvement of CADM1/TSLC1). (2016)
  • Author(s): 萩山満、米重あづさ、伊藤彰彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] がん抑制遺伝子CADM1による Cbpを介したSrc経路抑制機構の解析(Roles of cell adhesion molecule 1 (CADM1) in Cbp-dependent inactivation of c-Src pathway). (2016)
  • Author(s): 坪井裕見、尾山大明、秦裕子、伊藤彰彦、村上善則
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 肺上皮接着分子CADM1/TSLC1の細胞外切断亢進が特発性間質性肺炎における上皮アポトーシスの一因となる(Increased ectodomain shedding of CADM1/TSLC1 as a cause of epithelial apoptosis in idiopathic interstitial pneumonia). (2016)
  • Author(s): 米重あづさ、萩山満、伊藤彰彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 接着分子cell adhesion molecule 1の細胞内断片による肺上皮アポトーシス誘導：肺気腫発症への関与(Induction of lung epithelial cell apoptosis in emphysema by the intracellular domain of cell adhesion molecule 1) (2015)
  • Author(s): 萩山満、米重あづさ、伊藤彰彦
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-09
• [Presentation] 上皮性癌種の肉腫様変化では骨肉腫／骨芽細胞様表現型が出現する(Manifestation of osteoblastic phenotypes in the sarcomatous components of epithelial carcinoma) (2015)
  • Author(s): 米重あづさ、村上哲平、西村俊司、伊藤彰彦
  • Organizer: 第７４回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 肺癌の表層壊死部にアスペルギルスの腐生が認められた1例（Colonization of Aspergillus on the necrotic surface of lung cancer） (2015)
  • Author(s): 榎木英介、伊藤彰彦、他
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-05-02
• [Presentation] 特発性間質性肺炎における肺上皮接着分子CADM1の発現異常（Aberrant expression of lung-epithelial cell adhesion molecule 1 in idiopathic interstitial pneumonia） (2015)
  • Author(s): 米重あづさ、伊藤彰彦、他
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-05-02
• [Presentation] アクチン結合性アダプター蛋白α-parvinは偽足突起に局在し、小葉乳癌のリンパ節転移に関与する（Involvement of alpha-parvin, a pseudopodial constituent, in lobular breast carcinoma metastasis） (2015)
  • Author(s): 萩山満、伊藤彰彦、他
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-05-01
• [Presentation] ２型糖尿病患者の膵島における接着分子CADM1は細部外ドメインの切断が亢進している（Increased ectodomain shedding of CADM1 from pancreatic islets in type2 deabetes mellitus） (2015)
  • Author(s): 井上敬夫、伊藤彰彦、他
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30
• [Remarks] 近畿大学医学部病理学講座
  • URL: http://www.med.kindai.ac.jp/patho/
• [Patent(Industrial Property Rights)] 培養装置及び該培養装置を用いた細胞培養法 (2015)
  • Inventor(s): 伊藤彰彦
  • Industrial Property Rights Holder: 伊藤彰彦
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-087897
  • Filing Date: 2015-04-22