野村 慎太郎
(のむら・しんたろう)
Shintaro Nomura
略歴
- 東京大学大学院農学研究科博士課程修了
- 東京大学応用微生物研究所酵素学研究部門助手、大阪大学医学部病理学講座准教授、同大学院生命機能研究科時空生物学講座准教授を経て本学へ
硬組織修復、再生の分子機構解析
石灰化をともなう病気の発生機序解析
発生工学的手法を用いたオステオポンチンの機能解析
- 研究の応用領域
- 再生医療、臓器構築、リハビリテーション
- 産官学連携で求めるパートナー
- 整形外科学、形成外科学の基礎、臨床研究者。リハビリテーション関連機器開発研究者
Osteopontin is one of the major extracellular matrix proteins in bone and cartilage. It contains calcium binding domain(s) and RGD-motif which act as integrin binding domain and acts as calcium binding cell adhesion molecule. Strong expression of osteopontin is detected in the process of development especially in the bone and kidney. Although the expression become undetectable soon after birth, dramatical expression of osteopontin is observed in the process of fracture healing. The spliced expression of osteopontin remind us a classic morphological findings that “Tissue regeneration process is a reincarnation of development”.
Strong expression of osteopontin is detected not only in the process of physiological but pathological calcification such as atherosclerosis, breast cancer and urinary calculus. Identification of the cells which express osteopontin mRNA in the pathological calcification was carried out by means of in situ hybridization. Knockout mice carrying disrupted osteopontin gene showed abnormal urinary calculus and survival rate in comapared to wild-type mice by the abdominal injection of oxalate. These results strongly suggest that osteopontin is involved in the pathological calcification. Furthermore, we could possibly utilize osteopontin for diagnosis, preventation and treatment in the future.
We identified tissue-specific and developmental stage-specific promoter regions of osteopontin by generating transgenic mice using GFP as a reporter gene. These transgenic mice were also used as experimental model animals for investigating the molecular mechanism of pathological calcification.
Iwahori K, Serada S, Fujimoto M, Ripley B, Nomura S, Mizuguchi H, Shimada K, Takahashi T, Kawase I, Kishimoto T, Naka T. SOCS-1 gene delivery cooperates with cisplatin plus pemetrexed to exhibit preclinical antitumor activity against malignant pleural mesothelioma. Int J Cancer. 132, 459-71. (2013).
Chean T, Konnno T, Egashira M, Bai R, Nmoura N, Nomura S, Sakurai T, Imakawa K. Estrogen-dependent uterine secretion of osteopontin activates blastocyst adhesion competence. PLoS One 7, e48933. (2012).
F. Terabe, M. Fujimoto, S. Serada, S. Shinzaki, H. Iijima, M. Tsuji, N. Hayashi, S. Nomura, H. Kawahata, M-H Jang, M. Miyasaka, M. Mihara, Y. Ohsugi, T. Kishumoto, T. Naka. Comparative analysis of the ef f ects of anti-IL-6 receptor mAb and anti-TNF mAb treatment on CD4(+) T-cell responses in murine colitis. Inf lamm Bowel Dis. 17, 491-502. (2011)
K. Iwahori, S. serada, M. Fujimoto, S. Nomura, T. Ozaki, CM Lee, H. Mizuguti, T. Takahashi, B. Ripley, M. Okumura, I. Kawase, T. Kishimoto, T. Naka. Overexpression of SOCS3 exhibits preclinical antitumor activity against malignant pleural mesothelioma. Int J Cancer. 129, 1005-17. (2011)
H. Haruta, N. Ohguro, M. Fujimoto, S. Hohki, F. Terabe, S. Serada, S. Nomura, K. Nishida, T. Kishimoto, T. Naka. Blockade of interleukin-6 signaling suppresses not only Th17 but also interphotoreceptor retinoid binding protein-specif ic Th1 by promoting regulatory T cells in experimental autoimmune uveoretinitis. Invest. Ophthal. and Visual Sci. 52, 3264-71. (2011)