Elucidation of mechanisms for hepatic differentiation by HGF

• Project/Area Number: 21790673
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kumamoto University (2011); Kagoshima University (2009-2010)
• Principal Investigator: TAKAMI Yoichiro 熊本大学, 発生医学研究所, 厚労科研研究員 (10500473)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: HGF / iPS細胞 / 分化誘導 / ミトコンドリア / ips細胞 / 肝細胞増殖因子 / 肝内胚葉 / 脂肪酸代謝 / マイクロアレイ

Research Abstract

The purpose of this study is to elucidate the mechanisms for HGF-promoted hepatic differentiation from iPS cells which are still unknown. In this study, we found that (1) the characters of differentiated cells from iPS cells may change according to the generation procedures of iPS cells, and (2) mitochondrial functions were associated with the feature of differentiated cells and cellular reprogramming

Research Products

• [Journal Article] High serum thioredoxin levels were reduced after tonsillectomy in patients with IgA nephropathy (2012)
  • Author(s): Nosaki T, Uto H, Takami Y, Oku M, Fukumoto M, Mera K, Nishida C, Tokunaga K, Sogabe A, Oketani M, Ido A, Kurono Y, Tsubouchi H
  • Journal Title: Intern Med Volume: 51 Pages: 559-565
  • Peer Reviewed
• [Journal Article] High Serum Thioredoxin Levels Are Reduced after Tonsillectomy in Patients with IgA Nephropathy (2012)
  • Author(s): Tsuyoshi Nosaki, Hirofumi Uto, Yoichiro Takami, et al
  • Journal Title: Internal Medicine Volume: 51 Issue: 6 Pages: 559-565
  • DOI: 10.2169/internalmedicine.51.6021
  • NAID: 130002061912
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Serum manganese superoxide dismutase and thioredoxin levels are potential prognostic markers among patients with HCV-related hepatocellular carcinoma (2011)
  • Author(s): Tamai T, Uto H, Takami Y, Oda K, Saishoji A, Hashiguchi M, Kumagai K, Kure T, Mawatari S, Moriuchi A, Oketani M, Ido A, Tsubouchi H
  • Journal Title: World J Gastroenterol Volume: 17 Pages: 4890-4898
  • Peer Reviewed
• [Journal Article] Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compaired to dietary fat (2011)
  • Author(s): Tanoue S Uto H, Kumamoto R, Arima S, Hashimoto S, Nasu Y, Takami Y, Moriuchi A, Sakiyama T, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Pages: 163-168
  • Peer Reviewed
• [Journal Article] Clinical proteomics for liver disease : a promising approach for discovery of novel biomarkers (2011)
  • Author(s): Uto H, Kanmura S, Takami Y, Tsubouchi H
  • Journal Title: Proteome Sci Volume: 8 Pages: 70-70
  • Peer Reviewed
• [Journal Article] Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compaired to dietary fat (2011)
  • Author(s): Shirou Tanoue, Hirofumi Uto, Ryo Kumamoto, et al
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 407 Issue: 1 Pages: 163-168
  • DOI: 10.1016/j.bbrc.2011.02.131
  • Peer Reviewed
• [Journal Article] Serum manganese superoxide dismutase and thioredoxin levels are potential prognostic markers among patients with HCV-related hepatocellular carcinoma (2011)
  • Author(s): Tsutomu Tamai, Hirofumi Uto, Yoichiro Takami, et al
  • Journal Title: World Journal of Gastroenterology Volume: 17 Pages: 4890-4898
  • Peer Reviewed
• [Journal Article] Insulin-Like Growth Factor Binding Protein-1 levels are increased in patients with IgA nephropathy (2010)
  • Author(s): Tokunaga K, Uto H, Takami Y, Mera K, Nishida C, Yoshimine Y, Fukumoto M, Oku M, Sogabe A, Nosaki T, Moriuchi A, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Biochem Biophys Res Commun Volume: 399 Pages: 144-149
  • Peer Reviewed
• [Journal Article] Identification of a novel biomarker for oxidative stress induced by hydrogen peroxide in primary human hepatocytes using the 2-nitrobenzenesulfenyl chloride isotope labeling method (2010)
  • Author(s): Takami Y, Uto H, Tamai T, Sato Y, Ishida Y, Morinaga H, Sakakibara Y, Moriuchi A, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Hepatol Res Volume: 40 Pages: 438-445
  • NAID: 10027291800
  • Peer Reviewed
• [Journal Article] Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factor. induced proliferation of the human hepatic stellate cell line LI90 (2010)
  • Author(s): Takami Y, Uto H, Takeshita M, Kai H, Akamatsu E, Moriuchi A, Hasegawa S, Oketani M, Ido A, Kataoka H, Tsubouchi H
  • Journal Title: Hepatol Res Volume: 40 Pages: 337-345
  • NAID: 10027407999
  • Peer Reviewed
• [Journal Article] Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factor-induced proliferation of the human hepatic stellate cell line LI90. (2010)
  • Author(s): Takami Y, Uto H, et al
  • Journal Title: Hepatology Research Volume: 40 Pages: 337-345
  • NAID: 10027407999
  • Peer Reviewed
• [Journal Article] Identification of a novel biomarker for oxidative stress induced by hydrogen peroxide in primary human hepatocytes using the 2-nitrobenzenesulfenyl chloride isotope labeling method. (2010)
  • Author(s): Takami Y, Uto H, et al
  • Journal Title: Hepatology Research Volume: 40 Pages: 438-445
  • NAID: 10027291800
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy. (2010)
  • Author(s): Tokunaga K, Uto H, et al
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 399 Pages: 144-149
  • Peer Reviewed
• [Journal Article] Clinical proteomics for liver disease : a promising approach for discovery of novel biomarkers. (2010)
  • Author(s): Uto H, Kanmura S, et al
  • Journal Title: Proteome Science Volume: 8 Pages: 70-79
  • Peer Reviewed
• [Journal Article] Proanthocyanidin derived from the leaver of Vaccinium virgatum suppresses platelet-derived growth factro-induced proliferation of the human hepatic stellate cell line LI90 (2010)
  • Author(s): Yoichiro Takami
  • Journal Title: Hepatology Research 40 Pages: 337-345
  • Peer Reviewed
• [Journal Article] Identification of a novel biomarker for oxidative stress induced by hydrogen peroxide in primary human hepatocytes using the 2-nitrobenzenesulfenyl chloride isotope labeling method (2010)
  • Author(s): Yoichiro Takami
  • Journal Title: Hepatology Research 40 Pages: 338-345
  • NAID: 10027291800
  • Peer Reviewed
• [Journal Article] 肝発癌予防につながる高機能性食品の探索 (2009)
  • Author(s): 宇都浩文、高見陽一郎、坪内博仁
  • Journal Title: Functional Food Volume: Vol.3 Pages: 150-154
• [Presentation] 難治性疾患由来外来因子フリーiPS細胞の樹立 (2012)
  • Author(s): 高見陽一郎、山田祥慎、片山朋彦、濱崎誠、房木ノエミ、江良択実
  • Organizer: 第8回宮崎サイエンスキャンプ
  • Place of Presentation: シーガイアコンベンションセンター(宮崎)
  • Year and Date: 2012-02-18
• [Presentation] Serum manganese superoxide dismutase and thioredoxin levels may predict mortality in patients with hepatitis C virus-related hepatocellular carcinoma (2011)
  • Author(s): Tamai T, Uto H, Takami Y, Oda K, Saishoji A, Hashiguchi M, Kure T, Kumagai K, Mawatari S, Moriuchi A, Oketani M, Ido A, Tsubouchi H
  • Organizer: The International Liver Cancer Association 2011 Fifth Annual Conference
  • Place of Presentation: Hong Kong Convention and Exhibition Centre(Hong Kong, China)
  • Year and Date: 2011-09-03
• [Presentation] Serum manganese superoxide dismutase and thioredoxin levels may predict mortality in patients with hepatitis C virus-related hepatocellular carcinoma (2011)
  • Author(s): Tsutomu Tamai, Hirofumi Uto, Yoichiro Takami, et al
  • Organizer: The International Liver Cancer Association 2011 Fifth Annual Conference
  • Place of Presentation: Hong Kong Convention and Exhibition Centre (Hong Kong)
  • Year and Date: 2011-09-03
• [Presentation] Clinical significance of serum MnSOD levels in patients with hepatitis C virus(HCV)-related chronic liver disease (2010)
  • Author(s): Tamai T, Uto H, Takami Y, Saishoji A, Hashiguchi M, Kumagai K, Kure T, Mawatari S, Moriuchi A, Oketani M, Ido A, Tsubouchi H
  • Organizer: The 7th APASL Single Topic Conference "Hepatitis C Virus"
  • Place of Presentation: Makuhari Messe(Chiba, Japan)
  • Year and Date: 2010-12-18
• [Presentation] 誘導型多能性幹細胞(iPS細胞)は肝細胞への分化過程で脂肪化した肝細胞様細胞を生じる (2010)
  • Author(s): 高見陽一郎、宇都浩文、佐藤悠子、熊谷公太郎、呉建、玉井努、森内昭博、嵜山敏男、桶谷真、井戸章雄、坪内博仁
  • Organizer: 第42回日本臨床分子形態学会・学術集会
  • Place of Presentation: 東レ総合研修センター(静岡)
  • Year and Date: 2010-09-25
• [Presentation] 誘導型多能性幹細胞(ips細胞)は肝細胞への分化過程で脂肪化した肝細胞様細胞を生じる (2010)
  • Author(s): 高見陽一郎、宇都浩文, 他
  • Organizer: 第42回日本臨床分子形態学会・学術集会
  • Place of Presentation: 三島市
  • Year and Date: 2010-09-25
• [Presentation] ALTが正常を持続するC型肝炎ウイルス持続感染者の血清プロテオミクス (2010)
  • Author(s): 佐藤悠子、宇都浩文、高見陽一郎、佐々木文郷、熊谷公太郎、最勝寺晶子、小田耕平、呉建、馬渡誠一、玉井努、森内昭博、桶谷真、井戸章雄、中島知明、岡上武、坪内博仁
  • Organizer: 日本プロテオーム学会2010年会
  • Place of Presentation: 東京ベイホテル東急(東京)
  • Year and Date: 2010-07-26
• [Presentation] 腸管マクロファージに発現するオステオアクチビンは腸炎を軽減する (2010)
  • Author(s): 佐々木文郷、井戸章雄、高見陽一郎、熊谷公太郎、岩下祐司、指宿和成、隈元亮、上村修司、嵜山敏男、宇都浩文、桶谷真、坪内博仁
  • Organizer: 第47回日本消化器免疫学会総会
  • Place of Presentation: 大津プリンスホテル(滋賀)
  • Year and Date: 2010-07-08
• [Presentation] 血清MnSODは非アルコール性脂肪肝炎とHCV関連慢性肝疾患のバイオマーカーである (2010)
  • Author(s): 高見陽一郎、宇都浩文, 他
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形市
  • Year and Date: 2010-05-28
• [Presentation] 血清MnSODは非アルコール性脂肪肝炎とHCV関連慢性肝疾患のバイオマーカーである (2010)
  • Author(s): 高見陽一郎、宇都浩文、玉井努、最勝寺晶子、橋口正史、熊谷公太郎、呉建、馬渡誠一、森内昭博、桶谷真、井戸章雄、佐藤悠子、中島知明、岡上武、坪内博仁
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: ホテルメトロポリタン山形(山形)
  • Year and Date: 2010-05-27
• [Presentation] Hepatocyte growth factor stimulates the migration of gastric epithelial cells by altering the intracellular localization of the tight junction protein ZO-1 Digestive Disease Week(DDW) 2010 (2010)
  • Author(s): Nasu Y, Ido A, Tanoue S, Hashimoto S, Sasaki F, Takami Y, Kanmura S, Setoyama H, Funakawa K, Moriuchi A, Sakiyama T, Uto H, Oketani M, Tsubouchi H
  • Organizer: New Orleans Ernest N. Morial Convention Center
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2010-05-01
• [Presentation] 炎症性腸疾患における炎症のフィードバック調節因子osteoactivinの役割の解明 (2010)
  • Author(s): 佐々木文郷、井戸章雄、高見陽一郎、熊谷公太郎、上村修司、森内昭博、嵜山敏男、宇都浩文、桶谷真、坪内博仁
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 朱鷺メッセ(新潟)
  • Year and Date: 2010-04-22
• [Presentation] 血清MnSOD濃度の非アルコール性脂肪性肝疾患における臨床的有用性の検討 (2009)
  • Author(s): 高見陽一郎
  • Organizer: 第17回日本消化器関連学会週間
  • Place of Presentation: 京都
  • Year and Date: 2009-11-15
• [Presentation] The serum levels of manganese superoxide dismutase(MnSOD) are elevated in patients with non-alcoholic steatohepatitis(NASH) American Association for the Study of Liver Diseases(AASLD) 60th The Liver Meeting 2009 (2009)
  • Author(s): Takami Y, Uto H, Tamai T, Satoh Y, Moriuchi A, Funakawa K, Sakiyama T, Oketani M, Ido A, Nakajima T, Okanoue T, Tsubouchi H
  • Organizer: Hynes Convention Center
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-11-02
• [Presentation] The serum levels of manganese superoxide dismutase (MnSOD) are elevated in patients with non-alcoholic steatohepatitis (NASH) (2009)
  • Author(s): Yoichiro Takami
  • Organizer: American Association for the Study of Liver Diseases (AASLD) 60th The Liver Meeting 2009
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-11-01
• [Presentation] 血清MnSOD濃度の非アルコール性脂肪性肝疾患における臨床的有用性の検討 (2009)
  • Author(s): 高見陽一郎、宇都浩文、玉井努、佐藤悠子、熊谷公太郎、呉建、馬渡誠一、森内昭博、長谷川将、桶谷真、井戸章雄、中島知明、岡上武、坪内博仁
  • Organizer: 第17回日本消化器関連学会週間
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2009-10-15
• [Presentation] Proanthocyanidinはplatelet-derived growth factorによる肝星細胞の活性化を抑制する (2009)
  • Author(s): 高見陽一郎、宇都浩文、竹下正彦、甲斐久博、赤松絵奈、森内昭博、長谷川将、桶谷真、井戸章雄、片岡寛章、坪内博仁
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸ポートピアホテル(神戸)
  • Year and Date: 2009-06-05
• [Presentation] Proanthocyanidinはplatelet-derived growth factorによる肝星細胞の活性化を抑制する (2009)
  • Author(s): 高見陽一郎
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Patent(Industrial Property Rights)] 肝線維化抑制剤 (2011)
  • Inventor(s): 高見陽一郎、坪内博仁、宇都浩文、片岡寛章、竹下正彦
  • Industrial Property Rights Holder: 財団法人宮崎県産業支援財団、国立大学法人鹿児島大学、国立大学法人宮崎大学、南日本酪農協同株式会社
  • Acquisition Date: 2011-09-16
• [Patent(Industrial Property Rights)] 非アルコール性脂肪性肝炎を推定するための検出方法 (2009)
  • Inventor(s): 坪内博仁、宇都浩文、岡上武、高見陽一郎
  • Industrial Property Rights Holder: 財団法人宮崎県産業支援財団、国立大学法人鹿児島大学
  • Industrial Property Number: 2009-131853
  • Filing Date: 2009-06-01
• [Patent(Industrial Property Rights)] 非アルコール性脂肪性肝炎を推定するための検出方法 (2009)
  • Inventor(s): 高見陽一郎
  • Industrial Property Rights Holder: 財団法人宮崎県産業支援財団
  • Industrial Property Number: 2009-131853
  • Filing Date: 2009-06-01