Development of in vitro NASH model using hepatocyte spheroid.

• Project/Area Number: 18590735
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Okayama University
• Principal Investigator: SHIRAHA Hidenori (2007) Okayama University, University Hospital, Assistant Professor (40379748); 真治 紀之 (2006) 岡山大学, 医学部・歯学部附属病院, 講師 (70314680)
• Co-Investigator(Kenkyū-buntansha): KOIDE Norio Okayama University, Graduate Schcol of Medicine, Dentistry and Pharmaceutical Science, Professor (20142333) ; 白羽 英則 岡山大学, 医学部・歯学部附属病院, 助手 (40379748)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,550,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: hepatocellular spheroids / NASH / adipogenesis

Research Abstract

Mouse fibroblast 3T3-L1 was able to be adipogenetic by IBMX and dexamethason under DMEM+FBS condition. We have tried to form spheroid with 3T3-L1. 3T3-L1 did not form spheroid under Williams E medium with insulin and EGF. To solve this problem, we tried two alternative ways. 1. To enhance EGF signaling, we utilized NIH3T3 cells with EGFR. These cells did not form spheroid. 2. To control cell-cell contact, a tumor suppresser gene was introduced into cells. Introduction of RUNX3 cDNA enhanced cell-cell contact of 3T3 cells. E-cadherin expression was increased in RUNX3 transfected cells.increased in RUNX3 transfected cells. While N-cadherin expression was decreased in these cells. RUNX3 introduced 3T3 was able to form spheroid. These cells may be a useful in vitro model for NASH.

Research Products

• [Journal Article] Hepatitis B Virus DNA in Liver Tissue and Risk for Hepatocarcinogenesis in Patients with Hepatitis C Virus-Related Chronic Liver Disease. A Prospective Study. (2008)
  • Author(s): Obika M, Shinji T, Fujioka SI, Terada R, Ryuko H, Lwin AA, Shiraha H, Koide N
  • Journal Title: Intervirology 51(1) Pages: 59-68
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatitis B Virus DNA in Liver Tissue and Risk for Hepatocarcinogenesis in Patients with Hepatitis C Virus-Related Chronic Liver Disease. A Prospective Study (2008)
  • Author(s): Obika, M., Shinji, T., Fujioka, SI., Terada, R., Ryuko, H., Lwin, AA., Shiraha, H., Koide. N
  • Journal Title: Intervirology 51-1 Pages: 59-68
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatitis B Virus DNA in Liver Tissue and Risk for Hepatocarcinogenesis in Patients with Hepatitis C Virus-Related Chronic Liver Disease. A Prospective Study. (2008)
  • Author(s): Obika M, Shinji T, Fujioka SI, Terada R, Ryuko H, Lwin AA, Shiraha H, Koide N.
  • Journal Title: Intervirology 51(1) Pages: 59-68
  • Peer Reviewed
• [Journal Article] Cimetidine inhibits epidermal growth factor-induced cell signaling (2007)
  • Author(s): Fujikawa T, Shiraha H, et. al.
  • Journal Title: J Gastroenterol Hepatol. 22(3) Pages: 436-443
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Des-gamma -carboxy prothrombin-promoted vascular endothelial cell proliferation and migration. (2007)
  • Author(s): Fujikawa T, Shiraha H, Ueda N, Takaoka N, Nakanishi Y, Matsuo N, Tanaka S, Nishina SI, Suzuki M, Takaki A, Sakaguchi K, Shiratori Y.
  • Journal Title: J Biol Chem. 282(12) Pages: 8741-8
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatitis C Virus Genotype Distribution in Myanmar: Predominance of Genotype 6 and Existence of New Genotype 6 Subtype (2007)
  • Author(s): Lwin AA, Shinji T, Koide N, et. al.
  • Journal Title: Hepatology Research 37(5) Pages: 337-45
  • NAID: 10020163893
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Decreased expression of hMLH1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells. (2007)
  • Author(s): Fujita H, Shiraha H, et. al.
  • Journal Title: Oncology Reports 18(5) Pages: 59-68
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Oral administration of taurine improves experimental pancreatic fibrosis. (2007)
  • Author(s): Shirahige A, Koide N, et. al.
  • Journal Title: Journal of Gastroenterology and Hepatology 23(2) Pages: 321-327
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] カルボキシラーゼ遺伝子異常と肝癌増殖 (2007)
  • Author(s): 白羽英則、他
  • Journal Title: Minophagen Medical Review 52(2) Pages: 144-145
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 腫瘍マーカーの分子機能はどこまで解っているのか 異常プロトロンビンの肝細胞癌進展における役割 (2007)
  • Author(s): 白羽英則、他
  • Journal Title: 日本臨床検査自動化学会会誌 32(2) Pages: 164-165
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 【PIVKA-IIの新しい展開】PIVKA-IIの基礎 PIVKA-IIと細胞増殖 (2007)
  • Author(s): 白羽英則、他
  • Journal Title: 肝・胆・膵 54(4) Pages: 477-481
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 生活習慣病と臨床検査 アルコール多飲の線維化マーカー (2007)
  • Author(s): 水島孝明, 越智浩二, 小出典男
  • Journal Title: 臨床病理 55(8) Pages: 751-757
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cimetidine inhibits epidermal growth factor-induced cell signaling (2007)
  • Author(s): Fujikawa, T., Shiraha, H., et. al.
  • Journal Title: Journal of Gastroenterology and Hepatology 22-3 Pages: 436-43
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Des-gamma -carboxy prothrombin-promoted vascular endothelial cell proliferation and migration (2007)
  • Author(s): Fujikawa, T., Shiraha, H., Ueda, N., Takaoka, N., Nakanishi, Y., Matsuo, N., Tanaka, S., Nishina, SI., Suzuki, M., Takaki, A., Sakaguchi, K., Shiratori, Y
  • Journal Title: Biol Chem 282-12 Pages: 8741-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatitis C Virus Genotype Distribution in Myanmar : Predominance of Genotype 6 and Existence of New Genotype 6 Subtype (2007)
  • Author(s): Lwin, AA., Shinji, T., Koide, N., et. al.
  • Journal Title: Hepatology Research 37-5 Pages: 337-45
  • NAID: 10020163893
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Decreased expression of hMLH1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells (2007)
  • Author(s): Fujita, H., Shiraha, H., et. al.
  • Journal Title: Oncology Reports 18-5 Pages: 59-68
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Oral administration of taurine improves experimental pancreatic fibrosis (2007)
  • Author(s): Shirahige, A., Koide, N., et. al.
  • Journal Title: Journal of Gastroenterology and Hepatology 23-2 Pages: 321-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Variant carvoxylase contributes hepatocellular carcinoma progression (in Japanese) (2007)
  • Author(s): Shiraha, H., et. al.
  • Journal Title: Minophagen Medical Review 52-2 Pages: 144-5
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Des-gamma carboxy prothrombin contributes hepatocellular carcinoma progression (in Japanese) (2007)
  • Author(s): Shiraha, H., et. al.
  • Journal Title: JACLA Journal 32-2 Pages: 164-5
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Des-gamma carboxy prothrombin and cellproliferation(in Japanese) (2007)
  • Author(s): Shiraha, H., et. al.
  • Journal Title: Liver Billiary Pancreas 54-4 Pages: 477-81
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fibrosis marker for alcohol drinker(in Japanese) (2007)
  • Author(s): Mizushima, T., Ochi, K., Koide, N
  • Journal Title: Clinical Pathology 55-8 Pages: 751-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] カルボキシラーゼ遺伝子異常と肝癌増殖 (2007)
  • Author(s): 白羽英則, 他
  • Journal Title: Minophagen Medical Review 52(2) Pages: 144-145
• [Journal Article] 腫瘍マーカーの分子機能はどこまで解っているのか 異常プロトロンビンの肝細胞癌進展における役割 (2007)
  • Author(s): 白羽英則, 他
  • Journal Title: 日本臨床検査自動化学会会誌 32(2) Pages: 164-165
• [Journal Article] 【PIVKA-IIの新しい展開】 PIVKA-IIの基礎 PIVKA-IIと細胞増殖 (2007)
  • Author(s): 白羽英則, 他
  • Journal Title: 肝・胆・膵 54(4) Pages: 477-481
• [Journal Article] Cimetidine inhibits epidermal growth factor-induced cell signaling (2007)
  • Author(s): Fujikawa T, Shiraha H, et al.
  • Journal Title: J Gastroenterol Hepatol. 22.3 Pages: 436-443
• [Journal Article] Des-gamma -carboxy prothrombin-promoted vascular endothelial cell proliferation and migration. (2007)
  • Author(s): Fujikawa T, Shiraha H, et al.
  • Journal Title: J Biol Chem. (印刷中)
• [Journal Article] Hepatitis C Virus Genotype Distribution in Myanmar : Predominance of Genotype 6 and Existence of New Genotype 6 Subtype (2007)
  • Author(s): Lwin AA, Shinji T, Koide N, et al.
  • Journal Title: Hepatology Research (印刷中)
  • NAID: 10020163893
• [Journal Article] Three Type 6 Hepatitis C Virus Subgroups among Blood Donors in the Yangon Area of Myanmar Are Identified as Subtypes 6m and 6n, and a Novel Subtype by Sequence Analysis of the Core Region. (2006)
  • Author(s): Shinji T, Lwin AA, Koide N, et. al.
  • Journal Title: Acta Med Okayama. 60(6) Pages: 345-349
  • NAID: 120002305493
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] どうする?パニック値 生化学 9.アンモニア濃度高値 (2006)
  • Author(s): 真治紀之、小出典男
  • Journal Title: 検査と技術 34(6) Pages: 550-551
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Three Type 6 Hepatitis C Virus Subgroups among Blood Donors in the Yangon Area of Myanmar Are Identified as Subtypes 6m and 6n, and a Novel Subtype by Sentience Analysis of the Core Reeion (2006)
  • Author(s): Shinji, T., Lwin, AA., Koide, N., et. al.
  • Journal Title: Acta Med Okayama 60-6 Pages: 345-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] How to deal with high serum ammonia (in Japanese) (2006)
  • Author(s): Shinji, T., Koide, N
  • Journal Title: Labmedicin and Tequnique 282-12 Pages: 8741-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Panic value in laboratory data (in Japanese) (2006)
  • Author(s): Shinji, T., Koide, N
  • Journal Title: Chugai Igaku Pages: 999-999
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Three Type 6 Hepatitis C Virus Subgroups among Blood Donors in the Yangon Area of Myanmar Are Identified as Subtypes 6m and 6n, and a Novel Subtype by Sequence Analysis of the Core Region. (2006)
  • Author(s): Shinji T, Lwin AA, Koide N, et al.
  • Journal Title: Acta Med Okayama. 60.6 Pages: 345-349
  • NAID: 120002305493
• [Journal Article] どうする?パニック値 生化学 9.アンモニア濃度高値 (2006)
  • Author(s): 真治紀之, 小出典男
  • Journal Title: 検査と技術 34.6 Pages: 550-551
• [Presentation] Vitamin K依存性カルボキシラーゼ活性による肝癌細胞移動能制御 (2008)
  • Author(s): 白羽英則、他
  • Organizer: 第11回Vitamin K and aging研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-02-16
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Vitamin K dependent carboxylase suppress cell proliferation of hepatocellular carcinoma (2008)
  • Author(s): Shiraha, H., et. al.
  • Organizer: Meeting for vitamin K and aging
  • Place of Presentation: Tokyo
  • Year and Date: 2008-02-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Vitamin K依存性カルボキジラーゼ活性による肝癌細胞移動能制御 (2008)
  • Author(s): 白羽 英則、他
  • Organizer: 第11回Vitamin K and aging研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-02-16
• [Presentation] カルボキシラーゼの肝癌血管新生における意義 (2007)
  • Author(s): 白羽英則、他
  • Organizer: Japan Digestive Disease Week 2007
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-19
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Splice variant of gamma-glutamyl carboxylase contributes progression of hepatocellular carcinoma. (2007)
  • Author(s): Hidenori Shiraha, et. al.
  • Organizer: 日本癌学会第66回総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] RUNX3 inhibits cell migration in hepatocellular carcinoma cell line. (2007)
  • Author(s): Shigetomi Tanaka, Hidenori Shiraha, et. al.
  • Organizer: 日本癌学会第66回総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Splice variant of gamma-glutamyl carboxylase contributes progression of hepatocellular carcinoma (2007)
  • Author(s): Hidenori, Shiraha, et. al.
  • Organizer: The 66th annual meeting for Japanese Cancer Association
  • Year and Date: 2007-10-04
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] RUNX3 inhibits cell migration in hepatocellular carcinoma cell line (2007)
  • Author(s): Tanaka, S., Shiraha, H
  • Organizer: The 66th annual meeting for Japanese Cancer Association
  • Year and Date: 2007-10-04
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Des-gamma carboxy prothrombin promotes angiogenesis in hepatocellular carcinoma (2007)
  • Author(s): Shiraha, H., et. al.
  • Organizer: Japan Digestive Disease Week 2007
  • Place of Presentation: Kobe
  • Year and Date: 2007-09-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Des-gamma-carboxy prothrombin promotes progression of hepatodellular carcinoma (2007)
  • Author(s): Hidenori Shiraha, et. al.
  • Organizer: 35th Congress of the International Society for On codevelopmental Biology and Medicine
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2007-09-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Des-gamma-carboxy prothrombin promotes progression of hepatodellular carcinoma (2007)
  • Author(s): Hidenori, Shiraha, et. al.
  • Organizer: 35th Congress of the International Society for Oncodevelopmental Biology and Medicine
  • Place of Presentation: Prague
  • Year and Date: 2007-09-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Des-gamma-carboxy prothrombin promotes progression of hepatodellular carcinoma (2007)
  • Author(s): Hidenori Shiraha, et. al.
  • Organizer: 35th Congress of the International Society for Oncodevelopmental Biology and Medicine
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2007-09-15
• [Book] 検査値の見方-付 パニック値・警戒値- (2006)
  • Author(s): 中井利昭, 他 編集
  • Total Pages: 999
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 検査値の見方-付 パニック値・警戒値- (2006)
  • Author(s): 中井利昭 他 編集
  • Total Pages: 999
  • Publisher: 中外医学社