Global analysis for epigenetic alterations of hepatic stellate cells in the transformation using Gia-sequencing method.

• Project/Area Number: 20590370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: MASUDA Tomoyuki Iwate Medical University, 医学部, 教授 (10199698)
• Co-Investigator(Kenkyū-buntansha): MAESAWA Chihaya 岩手医科大学, 医学部, 教授 (10326647) ; OIKAWA Hiroki 岩手医科大学, 医, 講師 (50285582)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 肝 / 線維症 / 星細胞 / miRNA / epigenetics / 肝線維症 / 肝星細胞 / ギガシークエンサー / 肝炎 / 肝硬変 / エピジェネティックス

Research Abstract

We intensively examined on hepatic stellate cells (HSC) for the treatment strategy of liver fibrosis. The present study focused on epigenetic alterations within the process of HSCs transformation. Using Gia-base sequencing method, global alterations of DNA methylation were examined in HSC under the condition of HDAC inhibitor (TSA) and interferon (IFN)-γ. Of them, genes relating pluripotency of stem cells were altered, and the nucleus accumbens associated-1 (NACC1) might be an important factor along with cMYC and NANOG. These transition of HSC might be induced though epigenetic alterations.

Research Products

• [Journal Article] Down-regulation of microRNA-211 is involved in expression of preferentially expressed antigen of melanoma (PRAME) in melanoma cells. (2011)
  • Author(s): E. Sakaurai, C Maesawa
  • Journal Title: Int J Oncol in press
• [Journal Article] Accumbens-Associated 1 Contributes to Cortactin Deacetylation and Augments the Migration of Melanoma Cells. (2011)
  • Author(s): K. Tsunoda, H. Oikawa, H. Tada, Y. Tatemichi, S. Muraoka, S. Miura, M. Shibazaki, F. Maeda, K. Takahashi, T. Akasaka, T. Masuda, C. Maesawa, Nucleus
  • Journal Title: J Invest Dermatol in press
• [Journal Article] Nucleus accumbens-associated 1 contributes to cortactin deacetylation and augments the migration of melanoma cells. (2011)
  • Author(s): Tsunoda K
  • Journal Title: J Invest Dermatol Volume: 131(In press)
  • Peer Reviewed
• [Journal Article] Immunohistochemical Study of HER2 and TUBB3 Proteins in Extramammary Paget Disease. (2011)
  • Author(s): Miyamoto A
  • Journal Title: Am J Dermatopathol Volume: 33(In press)
  • Peer Reviewed
• [Journal Article] Non-invasive evaluation of liver fibrosis using acoustic radiation force impulse imaging in chronic hepatitis patients with hepatitis C virus infection. (2010)
  • Author(s): H. Kuroda, K. Kakisaka, Y. Tatemichi, K. Sawara, Y. Miyamoto, K. Oikawa, A. Miyasaka, Y. Takikawa, T. Masuda, K. Suzuki
  • Journal Title: Hepatogastroenterology 57 Pages: 1203-1207
• [Journal Article] Detection of human papillomavirus in a urothelial carcinoma mimicking urethral caruncle. (2010)
  • Author(s): Y. Tatemichi, H. Oikawa, C. Maesawa, J. Ambo, M. Sato, H. Koike, T. Sata, T. Fujioka, T. Masuda
  • Journal Title: Int J Urol 17 Pages: 189-191
  • NAID: 10027257188
• [Journal Article] Association of the TNF-{alpha}-C-857T polymorphism with resistance to the cholesterol-lowering effect of HMG-CoA reductase inhibitors in type 2 diabetic subjects. (2010)
  • Author(s): T. Takahashi, K. Takahashi, M. Yamashina, C. Maesawa, T. Kajiwara, H. Taneichi, N. Takebe, Y. Kaneko, T. Masuda, J. Satoh
  • Journal Title: Diabetes Care 33 Pages: 463-466
• [Journal Article] Expression profiles of nestin in vascular smooth muscle cells in vivo and in vitro. (2010)
  • Author(s): H. Oikawa, K. Hayashi, C. Maesawa, T. Masuda, K. Sobue
  • Journal Title: Exp Cell Res 316 Pages: 940-950
• [Journal Article] Immunohistochemical Study of HER2 and TUBB3 Proteins in Extramammary Paget Disease. (2010)
  • Author(s): A. Miyamoto, K. Akasaka, H. Oikawa, T. Akasaka, T. Masuda, C. Maesawa
  • Journal Title: Am J Dermatopathol
• [Journal Article] Non-invasive evaluation of liver fibrosis using acoustic radiation force impulse imaging in chronic hepatitis patients with hepatitis C virus infection. (2010)
  • Author(s): Kuroda H
  • Journal Title: Hepatogastroenterology Volume: 57 Pages: 1203-1207
  • Peer Reviewed
• [Journal Article] Association of the TNF-{alpha}-C-857T polymorphism with resistance to the cholesterol-lowering effect of HMG-CoA reductase inhibitors in type 2 diabetic subjects. (2010)
  • Author(s): Takahashi T, Takahashi K, Yamashina M, Maesawa C, Kajiwara T, Taneichi H, Takebe N, Kaneko Y, Masuda T, Satoh J.
  • Journal Title: Diabetes Care. 33 Pages: 463-466
  • Peer Reviewed
• [Journal Article] Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation. (2009)
  • Author(s): K. Yamauchi, H.M. Piao, T. Nakadate, T. Shikanai, Y. Nakamura, H. Ito, T. Mouri, H. Kobayashi, C. Maesawa, T. Sawai, H. Ohtsu, H. Inoue
  • Journal Title: Allergol Int 58 Pages: 125-134
  • NAID: 10025109331
• [Journal Article] Spontaneous [Ca2+]i oscillations in G1/S phase-synchronized cells. (2009)
  • Author(s): A.D. Russa, C. Maesawa, Y. Satoh
  • Journal Title: J Electron Microsc (Tokyo) 58 Pages: 321-329
• [Journal Article] Ontogeny of reticular framework of white pulp and marginal zone in human spleen : immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. (2009)
  • Author(s): T. Satoh, E. Sakurai, H. Tada, T. Masuda
  • Journal Title: Cell Tissue Res 336 Pages: 287-297
• [Journal Article] Differential microRNA expression between bone marrow side population cells and hepatocytes in adult mice. (2009)
  • Author(s): Y. Nagata, C. Maesawa, H. Tada, Y. Takikawa, A. Yashima-Abo, T. Masuda
  • Journal Title: Int J Mol Med 24 Pages: 35-43
• [Journal Article] Effect of atorvastatin on microRNA 221 / 222 expression in endothelial progenitor cells obtained from patients with coronary artery disease. (2009)
  • Author(s): Y. Minami, M. Satoh, C. Maesawa, Y. Takahashi, T. Tabuchi, T. Itoh, M. Nakamura
  • Journal Title: Eur J Clin Invest 39 Pages: 359-367
• [Journal Article] DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer. (2009)
  • Author(s): K. Kato, C. Maesawa, T. Itabashi, K. Fujisawa, K. Otsuka, S. Kanno, H. Tada, Y. Tatemichi, K. Kotani, H. Oikawa, T. Sugai, G. Wakabayashi, T. Masuda
  • Journal Title: Int J Oncol 35 Pages: 467-476
• [Journal Article] Loss of class III beta-tubulin induced by histone deacetylation is associated with chemosensitivity to paclitaxel in malignant melanoma cells. (2009)
  • Author(s): K. Akasaka, C. Maesawa, M. Shibazaki, F. Maeda, K. Takahashi, T. Akasaka, T. Masuda
  • Journal Title: J Invest Dermatol 129 Pages: 1516-1526
• [Journal Article] Differential microRNA expression between bone marrow side population cells and hepatocytes in adult mice (2009)
  • Author(s): Nagata Y, Maesawa C, Tada H, Takikawa Y, Yashima-Abo A, Masuda T.
  • Journal Title: Int J Mol Med 24 Pages: 35-43
  • Peer Reviewed
• [Journal Article] DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer. (2009)
  • Author(s): Kato K, Maesawa C, Itabashi T, Fujisawa K, Otsuka K, Kanno S, Tada H, Tatemichi Y, Kotani K, Oikawa H, Sugai T, Wakabayashi G, Masuda T.
  • Journal Title: Int J Oncol 35 Pages: 467-476
  • Peer Reviewed
• [Journal Article] Ontogeny of reticular framework of white pulp and marginal zone in human spleen : immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. (2009)
  • Author(s): Satoh T, Sakurai E, Tada H, Masuda T
  • Journal Title: Cell Tissue Res 336 Pages: 287-297
  • Peer Reviewed
• [Journal Article] Down-regulation of microRNA-127 is associated with overexpression of BCL6 protein in osteosarcoma cells. (2009)
  • Author(s): Masuda s, Maeasawa c, Nishida J, Masuda T, et al.
  • Journal Title: Cancer Sci 100(In press)
  • Peer Reviewed
• [Journal Article] Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. (2008)
  • Author(s): S. Mitomo, C. Maesawa, S. Ogasawara, T. Iwaya, M. Shibazaki, A. Yashima-Abo, K. Kotani, H. Oikawa, E. Sakurai, N. Izutsu, K. Kato, H. Komatsu, K. Ikeda, G. Wakabayashi, T. Masuda
  • Journal Title: Cancer Sci 99 Pages: 280-286
  • NAID: 10024002213
• [Journal Article] Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. (2008)
  • Author(s): N. Izutsu, C. Maesawa, M. Shibazaki, H. Oikawa, T. Shoji, T. Sugiyama, T. Masuda
  • Journal Title: Int J Oncol 32 Pages: 1227-1235
• [Journal Article] Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines. (2008)
  • Author(s): H. Itabashi, C. Maesawa, H. Oikawa, K. Kotani, E. Sakurai, K. Kato, H. Komatsu, H. Nitta, H. Kawamura, G. Wakabayashi, T. Masuda
  • Journal Title: Hepatol Res 38 Pages: 601-613
  • NAID: 10024148920
• [Journal Article] Angiotensin IT and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines. (2008)
  • Author(s): Itabashi H, Maesawa C, Masuda T.
  • Journal Title: Hepatol Res 38 Pages: 601-613
  • Peer Reviewed
• [Journal Article] Epigenetic modeification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. (2008)
  • Author(s): Izutsu N, Maesawa C, Masuda T., et al
  • Journal Title: Int J Oncol 32 Pages: 1227-1235
  • Peer Reviewed
• [Remarks] ホームページ等