The importance of EMT in RPE cells

• Project/Area Number: 26861457
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kumamoto University
• Principal Investigator: Takahashi Eri 熊本大学, 大学院生命科学研究部(医), 助教 (60622602)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 網膜色素上皮 / 上皮間葉転換 / TNF-α / ERMタンパク質ファミリー / ｐ３８MAPK / TAK1 / ＴＮＦ－α / ＥＲＭタンパク質ファミリー / ｐ３８ＭＡＰＫ / ＴＡＫ１ / 網膜色素上皮細胞 / Merlin

Outline of Final Research Achievements

Epithelial-mesenchymal transition (EMT) is associated with ocular fibrosis, especially proliferative vitreoretinopathy and subretinal fibrosis in age-related macular disease. We found that Merlin, one of ERM protein family, is essential for maintenance of epithelial phenotype in retinal pigment epithelial (RPE) cells. Tumor necrosis factor (TNF)-alpha is an inducer of EMT in RPE cells and TNF-α decreased the expression of Merlin, leading to phosphorlation of ERM proteins, p38MAPK via TAK1. TAK1-p38MAPK signaling pathway plays an important role in TNF-α-induced EMT in RPE cells.

Research Products

• [Journal Article] Effects of mechanical stress and vitreous samples in retinal pigment epithelial cells. (2016)
  • Author(s): Takahashi E, Fukushima A, Haga A, Inomata Y, Ito Y, Fukushima M, Tanihara H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 470 Issue: 3 Pages: 569-74
  • DOI: 10.1016/j.bbrc.2016.01.104
  • Peer Reviewed / Open Access
• [Journal Article] Differentiated Expression Patterns and Phagocytic Activities of Type 1 and 2 Microglia. (2016)
  • Author(s): Haga A, Takahashi E, Inomata Y, Kawahara K, Tanihara H.
  • Journal Title: Investigative Ophthalmology & Visual Sciences Volume: 57 Issue: 6 Pages: 2814-2823
  • DOI: 10.1167/iovs.15-18509
  • Peer Reviewed / Open Access
• [Journal Article] Merlin regulates the epithelial-to-mesenchymal transition of ARPE-19 cells via TAK1-p38MAPK-mediated activation. (2015)
  • Author(s): Takahashi E, Haga A, Tanihara H.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 56 Issue: 4 Pages: 2449-2458
  • DOI: 10.1167/iovs.14-16300
  • Peer Reviewed
• [Journal Article] Merlin Regulates Epithelial-to-Mesenchymal Transition of ARPE-19 cells via TAK1-p38MAPK-Mediated Activation (2015)
  • Author(s): Eri Takahashi, Akira haga, Hidenobu Tanihara
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 線維柱帯細胞における上皮間葉転換様現象 (2016)
  • Author(s): 高橋 枝里
  • Organizer: 第27回緑内障学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-09-07
• [Presentation] 眼疾患における上皮間葉転換とその制御 (2016)
  • Author(s): 高橋 枝里
  • Organizer: 第120回日本眼科学会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-09
• [Presentation] Two cases with scleral fixation of intraocular lens after trabeculectomy (2015)
  • Author(s): Eri Takahashi, Asaho Nishizawa, Toshihiro Inoue, Kazuyuki Kawabata, Hidenobu Tanihara
  • Organizer: 2015 ESCRS Annual Congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-09-05
  • Int'l Joint Research
• [Presentation] The effect of phacoemulsification on failure of trabeculectomy in uveitic glaucoma patients (2015)
  • Author(s): Asaho Nishizawa, Eri Takahashi, Saori Ohira, Keiichiro Iwao, Toshihiro Inoue, Hidenobu Tanihara
  • Organizer: 2015 ESCRS Annual Congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-09-05
  • Int'l Joint Research
• [Presentation] Merlin regulates hyaluronan endocytosis and epithelial mesenchymal transition in ARPE-19 cells (2015)
  • Author(s): Eri Takahashi, Akira Haga, Hidenobu Tanihara
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-03 – 2015-05-07
• [Presentation] Merlin regulates hyaluronan endocytosis and epithelial mesenchymal transition in ARPE-19 cells (2015)
  • Author(s): Eri Takahashi, Akira Haga, Hidenobu Tanihara
  • Organizer: 2015 ARVO Annual Congress
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] TGF--activated kinase 1 is essential for tumor necrosis factor--induced epithelial mesenchymal transition in ARPE-19 cells (2015)
  • Author(s): Koki Matsubara, Eri Takahashi, Akira Haga, Hidenobu Tanihara
  • Organizer: 2015 ARVO Annual Congress
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] 網膜色素上皮細胞におけるMerlinによるヒアルロン酸取り込みと上皮間葉転換の制御 (2015)
  • Author(s): 髙橋枝里、芳賀彰、谷原秀信
  • Organizer: 第１１９回日本眼科学会総会
  • Place of Presentation: 札幌、日本（ロイトン札幌、さっぽろ芸術文化の館、札幌市教育文化会館）
  • Year and Date: 2015-04-16 – 2015-04-19
• [Presentation] 網膜色素上皮細胞におけるMerlinによるヒアルロン酸取り込みと上皮間葉転換の制御 (2015)
  • Author(s): 高橋枝里、芳賀彰、谷原秀信
  • Organizer: 日本眼科学会
  • Place of Presentation: 札幌
  • Year and Date: 2015-04-07
• [Remarks] 熊本大学大学院 生命科学研究部 眼科学分野 研究内容 眼におけるEMT(上皮間葉転換）
  • URL: http://www2.kuh.kumamoto-u.ac.jp/ganka/kyousitu/naiyou/emt.html