Epithelial mesenchymal transition during airway remodeling

• Project/Area Number: 19590893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Mie University
• Principal Investigator: KOBAYASHI Tetsu Mie University, 医学部・附属病院, 医員 (20437114)
• Co-Investigator(Kenkyū-buntansha): TAGUCHI Osamu 三重大学, 医学部・附属病院, 講師 (90197244) ; ESTEBAN Gabazza 三重大学, 大学院・医学系研究科, 教授 (00293770)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: TGF-β / EMT / siRNA / 肺線維症 / 上皮間葉移行 / 気道リモデリング / 線維芽細胞

Research Abstract

線維化や組織修復のリモデリング過程において、線維芽細胞はその中心的役割を担う。今回Epithelial mesenchymal transition (EMT)の線維化に関する関与と制御方法を検討した。A549 細胞を用い、TGF-βによる刺激によってEMT 変化に関しての研究を実施。in vitro において、IL-1β、TNF-αとTGF-βの共刺激によってよりEMT が起こりやすいことを確認した。さらにブレオマイシン肺線維症モデルにおいて線維化に関与するsiRNA の投与によってin vivoにおいても線維化を抑制することを確認した。

Research Products

• [Journal Article] NF-kappaBmediates the survival of human bronchialepithelial cells exposed to cigarettesmoke extract (2008)
  • Author(s): Liu X, Togo S, Al-Mugotir M, Kim H,Fang Q, Kobayashi T, Wang X, Mao L,Bitterman P, Rennard S.
  • Journal Title: Respir Res 23;9 Pages: 66-66
  • Peer Reviewed
• [Journal Article] A prospective comparison of nursinghome-acquired pneumonia withhospital-acquired pneumonia innon-intubated elderly (2008)
  • Author(s): Maruyama T, Niederman MS,Kobayashi T, Kobayashi H, Takagi T,D'Alessandro-Gabazza CN, Fujimoto H, GilBernabe P, Hirohata S, Nakayama S,Nishikubo K, Yuda H, Yamaguchi A,Gabazza EC, Noguchi T, Takei Y, Taguchi O.
  • Journal Title: Respir Med 102(9) Pages: 1287-95
  • Peer Reviewed
• [Journal Article] RennardSI. Prostacyclin analogs stimulate VEGFproduction from human lung fibroblasts inculture (2008)
  • Author(s): Kamio K, Sato T, Liu X, Sugiura H, TogoS, Kobayashi T, Kawasaki S, Wang X, MaoL, Ahn Y, Holz O, Magnussen H.
  • Journal Title: Am J Physiol Lung Cell MolPhysiol 294(6)
  • Peer Reviewed
• [Journal Article] Role of the coagulation system in allergicinflammation in the upper airways (2008)
  • Author(s): Shimizu S, Shimizu T, Morser J,Kobayashi T, Yamaguchi A, Qin L, Toda M,D'Alessandro-Gabazza C, Maruyama T,Takagi T, Yano Y, Sumida Y, Hayashi T,Takei Y, Taguchi O, Suzuki K, Gabazza EC.
  • Journal Title: Clin Immunol 129(2) Pages: 365-71
  • Peer Reviewed
• [Journal Article] Roleof thrombin in interleukin-5 expressionfrom basophils (2008)
  • Author(s): Yamaguchi A, Gabazza EC, Takei Y,Yano Y, Fujimoto H, D'Alessandro-GabazzaCN, Murakami E, Kobayashi T, Takagi T,Maruyama J, Suzuki K, Taguchi O.
  • Journal Title: Biochem Biophys ResCommun 28 ; 368(1) Pages: 116-20
  • Peer Reviewed
• [Journal Article] Sphingosine 1-phosphate potentiateshuman lung fibroblast chemotaxis throughthe S1P2 receptor (2008)
  • Author(s): Hashimoto M, Wang X, Mao L,Kobayashi T, Kawasaki S, Mori N, ToewsML, Kim HJ, Cerutis DR, Liu X, Rennard SI.
  • Journal Title: Am J Respir Cell Mol Biol 39(3) Pages: 356-63
  • Peer Reviewed
• [Journal Article] PKCdelta mediates thrombin-augmentedfibroblast-mediated collagen gelcontraction (2008)
  • Author(s): Fang Q, Mao L, Kobayashi T, Wang X,Wyatt TA, Kim H, Liu X, Rennard SI
  • Journal Title: Biochem Biophys Res Commun 16;369(4) Pages: 1199-203
  • Peer Reviewed
• [Journal Article] Prostacycl in analogs stimulate VEGF production from human lung fibroblast in culture. (2008)
  • Author(s): Kamio K, Sato T, Liu X, Sugiura H, Togo S, Kobayashi T, et al.
  • Journal Title: Am J Physiol lung Cell Mol Physiol. 294 Pages: 1226-32
  • Peer Reviewed
• [Journal Article] Sphingosine 1-phosphate potentiates human lung fibroblast chemotaxis through the S1P2 receptor (2008)
  • Author(s): Hashimoto M, Wang X, Mao L, Kobavashi T, et al.
  • Journal Title: Am J Respir Cell Mol Biol. 39 Pages: 356-63
  • Peer Reviewed
• [Journal Article] PKC delta mediates thromb in-augmented fibroblast-mediated collagen gel contraction. (2008)
  • Author(s): Fang Q, Mao L, Kobayashi T, et al.
  • Journal Title: Biochem Biophys Res Commun. 369 Pages: 1199-203
  • Peer Reviewed
• [Journal Article] The CCchemokine ligand 2 (CCL2) mediatesfibroblast survival through IL-6 (2007)
  • Author(s): Liu X, Das AM, Seideman J, Griswold D,Afuh CN, Kobayashi T, Abe S, Fang Q, Hashimoto M, Kim H, Wang X, Shen L,Kawasaki S, Rennard SI
  • Journal Title: Am J Respir Cell Mol Biol 37(1) Pages: 121-8
  • Peer Reviewed
• [Journal Article] Prostacyclin analogs inhibit fibroblastcontraction of collagen gels through thecAMP-PKA pathway (2007)
  • Author(s): Kamio K, Liu X, Sugiura H, Togo S,Kobayashi T, Kawasaki S, Wang X, Mao L,AhnY, Hogaboam C, Toews ML, RennardSI
  • Journal Title: Am J Respir Cell Mol Biol 37(1) Pages: 113-20
  • Peer Reviewed
• [Journal Article] The CC chemokine ligand2 mediates fibroblast survival through IL-6 (2007)
  • Author(s): Liu X, Das AM, Seideman J, Griswold D, Afuh CN, Kobavashi T, et. al.
  • Journal Title: Am J Respir Cell Mol Biol. 37 Pages: 121-128
  • Peer Reviewed
• [Journal Article] Prostacyclin analogs inhibit fibroblast contraction of collagen gels Through the cAMP-PKA pathway (2007)
  • Author(s): Kamio K, Liu X, Sugiura H, TogoS, Kobayashi T, et.al.
  • Journal Title: Am J Respir Cell Mol Biol. 37 Pages: 113-120
  • Peer Reviewed
• [Journal Article] Prostaglandin E2 protects human lung fibroblasts from cigarette smoke Extractinduced apoptosis via EP2 receptor activation (2007)
  • Author(s): Sugiura H, Liu X. Togo S, Kobayashi T, et. al.
  • Journal Title: J Cell Physiol. 210 Pages: 99-110
  • Peer Reviewed
• [Presentation] Procoagulant and Anticoagulant Factors inPatients with Sleep Apnea (2009)
  • Author(s): M. Naito, T. Takagi, A. Fujiwara, A.Yamaguchi, T. Kobayashi, H. Kobayashi,C.N. D'Alessandro-Gabazza, J. Morser, E.C.Gabazza, Y. Takei, O. Taguchi
  • Organizer: ATS International Congress
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-05-18
• [Presentation] ProteinS Inhibits the Secretion of InflammatoryCytokines from Alveolar Epithelial Cells (2009)
  • Author(s): M. Naito, T. Takagi, A. Fujiwara, A.Yamaguchi, T. Kobayashi, H. Kobayashi,C.N. D'Alessandro-Gabazza , J. Morser,E.C. Gabazza, Y. Takei, O. Taguchi
  • Organizer: ATS International Congress
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-05-18
• [Presentation] Circulating Fibrocytes in Bronchial Asthma (2009)
  • Author(s): H. Kobayashi, M. Masuya, M. Naito, A.Fujiwara, T. Takagi, A. Yamaguchi, T.Kobayashi, E.C. Gabazza, O. Taguchi
  • Organizer: ATS International Congress
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-05-18
• [Presentation] 呼吸器疾患におけるsiRNA治療戦略 (2009)
  • Author(s): 小林哲, 他
  • Organizer: 第78回閉塞性肺疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-01-24
• [Presentation] 組織リモデリングにおけるMatrix metalloproteinase-9 の役割 (2008)
  • Author(s): 小林哲
  • Organizer: 第11回間質性肺炎細胞分子病態研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-23
• [Presentation] 組織りモデリングにおけるMMP-9の役割 (2008)
  • Author(s): 小林哲, 他
  • Organizer: 間質性肺炎細胞分子病態研究会
  • Place of Presentation: シェーンバッハ・サボー(東京)
  • Year and Date: 2008-08-23
• [Presentation] Matrixmetalloproteinase-9 modulates fibroblastactivity through autocrine TGF-b (2008)
  • Author(s): T.Kobayashi, et.al.
  • Organizer: 6th ERS Lung Science Conference
  • Place of Presentation: Estoril, Portugal
  • Year and Date: 2008-05-14
• [Presentation] Mmatrix metalloproteinase-9のリモデリングにおける役割 (2007)
  • Author(s): 小林 哲, 他.
  • Organizer: アレルギー・気道上皮細胞研究会第11回学術大会
  • Place of Presentation: シェーンバッハ・サボー(東京)
  • Year and Date: 2007-12-08