Lrig family controls corneal stem cell homeostasis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592621
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Doshisha University
• Principal Investigator: NAKAMURA Takahiro 同志社大学, 生命医科学部, 准教授 (30411078)
• Project Period (FY): 2011 – 2013
• Keywords: 上皮幹細胞 / 角膜 / EGFR / Lrig / 眼表面

Research Abstract

Corneal integrity and transparency is indispensable for good vision. The findings of this present study show that Lrig1 was highly expressed in the holoclone-type corneal epithelial stem cell population, and that Lrig1 was sporadically expressed in the basal cells of ocular-surface epithelium to regulate corneal epithelial cell fate during wound repair. Loss of Lrig1 resulted in impaired recruitment of stem cells post wounding, and in the cell-fate switch from transparent epithelium to keratinized skin-like epidermis, leading to corneal blindness. Lrig1 controlled corneal cell fate during repair by negatively regulating the STAT3-dependent inflammatory pathway, and blocking STAT3 rescued the pathological phenotypes observed in Lrig1 KO corneas. Here, we demonstrate that Lrig1 orchestrates corneal-tissue transparency and cell fate during repair.

Research Products

• [Journal Article] LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis (2014)
  • Author(s): Nakamura T, Hamuro J, Takaishi M, Simmons S, Maruyama K, Zaffalon A, Bentley AJ, Kawasaki S, Nagata-Takaoka M, Fullwood NJ, Itami S, Sano S, Ishii M, Barrandon Y, Kinoshita S
  • Journal Title: J Clin Invest. Volume: 124(1) Pages: 385-397
• [Journal Article] Corneal endothelial cell fate is maintained by LGR5 via the regulation of hedgehog and wnt pathway (2013)
  • Author(s): Hirata-Tominaga K*, Nakamura T*, Okumura N, Kawasaki S, Kay EP, Barrandon Y, Koizumi N, Kinoshita S
  • Journal Title: Stem Cells. Volume: 31(7) Pages: 1396-1407
• [Journal Article] 角膜の再生医療 (2013)
  • Author(s): 上野盛夫, 中村隆宏, 木下茂
  • Journal Title: 日本医師会雑誌 Volume: 142(4) Pages: 777-780
• [Journal Article] 眼科と幹細胞 (2013)
  • Author(s): 中村隆宏
  • Journal Title: 眼科 Volume: 55(3) Pages: 269-275
• [Journal Article] Sub-cellular spectrochemical imaging of isolated human corneal cells employing synchrotron radiation-based Fourier-transform infrared microspectroscopy (2013)
  • Author(s): Fogarty SW, Patel II, Trevisan J, Nakamura T, Hirschmugl C, Fullwood NJ, Martin FL
  • Journal Title: Analyst Volume: 138(1) Pages: 240-248
• [Journal Article] Visual improvement following cultivated oral mucosal epithelial transplantation (2013)
  • Author(s): Sotozono C, Inatomi T, Nakamura T, Koizumi N, Yokoi N, Ueta M, Matsuyama K, Miyakoda K, Kaneda H, Fukushima M, Kinoshita S
  • Journal Title: Ophthalmology Volume: 120(1) Pages: 193-200
• [Journal Article] 角膜と体性幹細胞 (2012)
  • Author(s): 木下茂, 中村隆宏
  • Journal Title: BIO Clinica Volume: 27(9) Pages: 17-21
• [Journal Article] 加齢による眼表面疾患の診断と治療 (2012)
  • Author(s): 木下茂, 中村隆宏
  • Journal Title: Advances in Aging and Health Research 2011 Pages: 145-149
• [Journal Article] 羊膜移植の適応と効果 (2012)
  • Author(s): 日野智之, 外園千恵, 稲富勉, 福岡秀記, 中村隆宏, 永田真帆, 小泉範子, 森和彦, 横井則彦, 木下茂
  • Journal Title: 日本眼科学会雑誌 Volume: 116(4) Pages: 374-378
• [Journal Article] Functional role of PPARδ in corneal epithelial wound healing. (2012)
  • Author(s): Nakamura Y, Nakamura T, Tarui T, Inoue J, Kinoshita S
  • Journal Title: Am J Pathol. Volume: 180(2) Pages: 583-598
• [Journal Article] Recent advances and future challenges in ocular surface reconstruction : On the road to translational medicine. (2012)
  • Author(s): Nakamura T, Inatomi T, Sotozono C, Koizumi N, Kinoshita S
  • Journal Title: Asia-Pacific Journal of Ophthalmology. January/February Volume: 1(1) Pages: 28-34
• [Journal Article] 角膜上皮の臨床解剖学と病態生理 (2011)
  • Author(s): 中村隆宏, 木下茂
  • Journal Title: 日本の眼科 Volume: 82(11) Pages: 1494-1499
• [Journal Article] Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease (2011)
  • Author(s): Takeda K, Nakamura T, Inatomi T, Sotozono C, Watanabe A, Kinoshita S.
  • Journal Title: Am J Ophthalmol Volume: 152(2) Pages: 195-201
• [Journal Article] New hopes and strategies for the treatment of severe ocular surface disease (2011)
  • Author(s): Nakamura T, Kinoshita S.
  • Journal Title: Curr Opin Ophthalmol Volume: 22(4) Pages: 274-278
• [Journal Article] Long-term results of autologous cultivated oralmucosal epithelial transplantation in the scar phase of severe ocular surface disorders. (2011)
  • Author(s): Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S
  • Journal Title: Br J Ophthalmol Volume: 95(7) Pages: 942-946
• [Presentation] 難治性眼表面疾患に対する培養鼻粘膜上皮シート移植術の開発 (2014)
  • Author(s): 小林正和, 永田真帆, 大倉翔貴, 中村隆宏, 小泉範子, 木下茂
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-03-06
• [Presentation] LRIG1による角膜の恒常性維持機構の解析 (2014)
  • Author(s): 中村隆宏, 羽室淳爾, 高石樹朗, 丸山和一, 永田真帆, 川崎論, 板見智, 佐野栄紀, 石井優, 木下茂
  • Organizer: 角膜カンファランス2014(第38回日本角膜学会総会・第30回日本角膜移植学会)
  • Place of Presentation: 沖縄
  • Year and Date: 2014-01-31
• [Presentation] 眼表面扁平上皮腫瘍におけるLRIG1発現解析 (2014)
  • Author(s): 永田真帆, 中村隆宏, 外園千恵, 稲富勉, 横井則彦, 木下茂
  • Organizer: 角膜カンファランス2014(第38回日本角膜学会総会・第30回日本角膜移植学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-01-31
• [Presentation] 角膜上皮細胞におけるR-spondin1の機能解 (2014)
  • Author(s): 大倉翔貴, 中村隆宏, 畑友衣子, 小林正和, 永田真帆, 小泉範子, 木下茂
  • Organizer: 角膜カンファランス2014(第38回日本角膜学会総会・第30回日本角膜移植学会)
  • Place of Presentation: 沖縄
  • Year and Date: 2014-01-31
• [Presentation] 難治性眼表面疾患に対する培養ヒト鼻粘膜上皮シート移植術の開発 (2014)
  • Author(s): 小林正和, 中村隆宏, 安田誠, 畑友衣子, 大倉翔貴, 岩本美優, 小泉範子, 久育男, 木下茂
  • Organizer: 角膜カンファランス2014(第38回日本角膜学会総会・第30回日本角膜移植学会)
  • Place of Presentation: 沖縄
  • Year and Date: 2014-01-31
• [Presentation] 難治性角結膜疾患に対する培養口腔粘膜上皮シート移植の橋渡し研究 (2013)
  • Author(s): 中村隆宏
  • Organizer: 第12回日本組織移植学会総会・学術集会
  • Place of Presentation: さいたま
  • Year and Date: 2013-08-03
• [Presentation] 難治性眼表面疾患に対する培養鼻粘膜上皮シートの開発 (2013)
  • Author(s): 小林正和, 中村隆宏, 安田誠, 畑友衣子, 大倉翔貴, 奥村直毅, 小泉範子, 久育男, 木下茂
  • Organizer: 角膜カンファランス2013(第37回日本角膜学会総会・第29回角膜移植学会)
  • Place of Presentation: 和歌山
  • Year and Date: 2013-02-15
• [Presentation] Recent advances and future challenges in ocular surface reconstruction. (2012)
  • Author(s): Nakamura T
  • Organizer: APAO/SOE Busan 2012
  • Place of Presentation: Busan Korea
  • Year and Date: 2012-04-14
• [Presentation] Recent advances and future challenges in ocular surface reconstruction. (2012)
  • Author(s): 中村隆宏
  • Organizer: 第116回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-06
• [Presentation] 結膜腫瘍でのLeucine-rich repeats and immunoglobulin-like domains 1(LRIG1)の発現 (2012)
  • Author(s): 永田真帆, 中村隆宏, 外園千恵, 稲富勉, 横井則彦, 板見智, 木下茂
  • Organizer: 第116回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-05
• [Presentation] 角膜扁平上皮癌におけるGPR49の発現の検討 (2012)
  • Author(s): 平田香菜, 中村隆宏, 外園千恵, 稲富勉, 奥村直毅, 小泉範子, 横井則彦, 木下茂
  • Organizer: 角膜カンファランス2012(第36回日本角膜学会総会・第28回日本角膜移植学会)
  • Place of Presentation: 東京
  • Year and Date: 2012-02-23
• [Presentation] 瘢痕性角結膜疾患と外科治療 (2012)
  • Author(s): 中村隆宏
  • Organizer: 第35回日本眼科手術学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-01-27
• [Presentation] Cultivated Oral Mucosal Epithelial Transplantation for Ocular Surface Reconstruction in Stevens-Johnson Syndrome (2011)
  • Author(s): Sotozono C, Inatomi T, Nakamura T, Ueta M, Yokoi N, Miyakoda K, Kinoshita S
  • Organizer: 第115回米国眼科学会議(AAO)
  • Place of Presentation: Orlando, USA
  • Year and Date: 2011-10-24
• [Presentation] 難治性角結膜疾患に対する自家培養口腔粘膜上皮シート移植のレトロスペクティブ調査 (2011)
  • Author(s): 外園千恵, 稲富勉, 中村隆宏, 小泉範子, 横井則彦, 都田桂子 ,松山琴音, 木下茂
  • Organizer: 第65回日本臨床眼科学会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-08
• [Presentation] 自家培養口腔粘膜上皮シート移植による結膜嚢再建効果の検討 (2011)
  • Author(s): 稲富勉, 外園千恵, 中村隆宏, 小泉範子, 都田桂子, 松山琴音, 木下茂
  • Organizer: 第65回日本臨床眼科学会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-08
• [Presentation] Long-Term Results of Cultivated Epithelial Transplantation for Severe Ocular Surface Dysfunction (2011)
  • Author(s): Nakamura T
  • Organizer: The Cornea and Tissue Engineering
  • Place of Presentation: Wales, Cardiff
  • Year and Date: 2011-08-19
• [Presentation] 屈折矯正後の重篤なMRSA角膜炎2症例 (2011)
  • Author(s): 外園千恵, 中村周, 中山琴美, 吉川晴菜, 中村隆宏, 稲富勉, 木下茂
  • Organizer: 第48回日本眼感染症学会
  • Place of Presentation: 京都
  • Year and Date: 2011-07-09
• [Presentation] 口腔組織を用いた角膜再生医療の現状と展望 (2011)
  • Author(s): 中村隆宏
  • Organizer: 第11回日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-05-27
• [Book] Non-ocular sources for cell-based ocular surface reconstruction. Ocular Surface Disease: Cornea, Conjunctiva and Tear Film, 1st Edition (2013)
  • Author(s): Nakamura T
  • Total Pages: 373-383