教授 吉岡秀克
研究テーマ コラーゲンの分子細胞生物学及び病理学
研究内容 一貫してコラーゲン分子に関する研究を行っています。コラーゲンは細胞外マトリックス分子の中でも最も豊富に存在し、体タンパクの約30%を占めています。現在、28種類の分子種及び45種類のa鎖をコードする遺伝子が見出されています。共通のGly-X-Y(X、Yは任意のアミノ酸)の構造を所有し、三重らせん構造の分子を形成し、さらに複数の分子と高分子会合体をとり、大小の線維の形成に関与しています。研究のスタートはVI型コラーゲンに対するモノクローナル抗体を作製し、免疫組織学的手法による解析でした。留学時に分子生物学的手法を学び、XI型及びXIX型コラーゲン遺伝子のクローニングを行いました。その後はこれらの遺伝子の発現、転写調節機構、シグナル伝達機構の解析を行っています。また、その機能解析のため、遺伝 子欠損マウスの解析を行いました。
現在、これらの研究は継続中である。また、動物モデルを用いた臓器線維症の機序の解明や、治療法の開発に向けた実験も進めています。
趣味 音楽鑑賞
ミシェル・ペトルシアーニ (Michel Petrucciani)
骨形成不全症の天才ジャス・ピアニスト 1962-1999)

1) Yano H, Hamanaka R, Nakamura-Ota M, Adachi S, Zhang JJ, Matsuo N, Yoshioka H: Sp7/Osterix induces the mouse pro-a2(I) collagen gene (Col1a2) expression via the proximal promoter in osteoblastic cells. BBRC 452, 531-536, 2014.
2) Hida M, Hamanaka R, Okamoto O, Yamashita K, Sasaki T, Yoshioka H, Matsuo N: Nuclear factor Y (NF-Y) regulates the proximal promoter activity of the mouse collagen  α1(XI) gene. In Vitro Cell Dev Biol – Animal 50, 358-366, 2014.
3) Nakamura-Ota M, Hamanaka R, Yano H, Adachi S, Sumiyoshi H, Matsuo N, and Yoshioka H. A new murine osteoblastic cell line immortalized with the SV40 large T antigen. Cell Tissue Bank 15:373-380, 2014
4) Yano H, Hamanaka R, Nakamura N, Sumiyoshi H, Matsuo N, Yoshioka H: Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis. BBRC 418, 457-463, 2012.
5) Wu Y-F, Matsuo N, Sumiyoshi H, Yoshioka H: Sp7/Osterix is involved in the up-regulation of the mouse pro-α1(V) collagen gene (Col5a1) in osteoblastic cells. Matrix Biol. 29, 701-706, 2010.
6) Wu, Y.F., Matsuo, N., Sumiyoshi, H., Yoshioka, H .: Sp7/Osterix up-regulates the mouse pro-a3(V) collagen gene (Col5a3) during the osteoblast differentiation. BBRC 394,  503-508, 2010
7) Hamada Y, Sumiyoshi H, Matsuo N, Yun-Feng W, Nakashima M, Yanagisawa S, Yoshioka H: The pro-a2(XI) collagen gene is expressed in odontoblasts. BBRC 392, 166-170, 2010.
8) Matsuo, N., Tanaka, S, Yoshioka, H, Gordon, M.K., Ramirez, F.: Collagen XXIV (Col24a1) gene expression is a specific marker of osteoblast differentiation and bone formation. Connect. Tissue Res. 49: 68-75, 2008
9) Matsuo, N, Tanaka, S, Gordon, M.K., Koch, M., Yoshioka, H., Ramirez, F.: CREB-AP1 protein complexes regulate transcription of the collagen XXIV gene (Col24a1) in osteoblast. J. Biol. Chem. 281: 5445-5452, 2006
10) Yamaguchi, K., Matsuo, N., Sumiyoshi, H., Fujimoto, N., Iyama, K.-I., Yanagisawa, S., Yoshioka, H.: The pro-α3(V) collagen chain is expressed in bone and its N-terminal basic peptide is adhesive to osteosarcoma cells. Matrix Biol: 24, 283-294, 2005
11) Sumiyoshi, H., Mor, N., Lee, S.Y., Doty, S., Henderson, S., Tanaka, S., Yoshioka, H., Rattan, S., Ramirez, F.: Esophageal muscle physiology and morphogenesis require assembly of a collagen XIX-rich basement membrane zone. J. Cell Biol. 166: 591-600, 2004
12) Nagato, H., Matsuo, N., Sumiyoshi, H., Sakata-Takatani, K., Nasu, M., Yoshioka, H.: The Transcription factor CCAAT-binding factor CBF/NF-Y and two repressors regulate the core promoter of the human pro-α3(V) collagen gene (COL5A3). J. Biol. Chem. 279: 46373-46383, 2004
13) Sakata-Takatani, K., Matsuo, N., Sumiyoshi, H., Tsuda, T., Yoshioka, H.: Identification of a functional CCAAT-like motif in the core promoter of the mouse pro-α1(V) collagen gene (Col5a1). Matrix Biol. 23: 87-99, 2004
14) Matsuo, N., Wang, Y.-H., Sumiyoshi, H., Sakata-Takatani, K., Nagato, H., Sakai, K., Sakurai, M., Yoshioka, H.: The transcription factor CCAAT-binding factor CBF/NF-Y regulates the proximal promoter activity in the human α1(XI) collagen gene (COL11A1). J. Biol. Chem. 278: 32763-32770, 2003
15) Iyama, K., Sumiyoshi, H., Khaleduzzaman, M., Matsuo, N., Yoshioka, H.: Differential expression of two exons of the α1(XI) collagen gene (Col11a1) in the mouse embryo. Matrix Biol. 20: 53-61, 2001
16) Sumiyoshi, H, Laub, F., Yoshioka, H., Ramirez, F.: Embryonic expression of type XIX collagen is transient and confined to muscle cells. Dev. Dyn. 220: 155-162, 2001
17) Kinoshita, A., Greenwel, P., Tanaka, S., Di Liberto, M., Yoshioka, H., Ramirez, F.: A transcription activator with restricted tissue distribution regulates cell-specific expression of α1(XI) collagen. J. Biol. Chem. 272: 31777-31784, 1997
18) Khaleduzzaman, M., Sumiyoshi, H., Ueki, Y., Inoguchi, K., Ninomiya, Y., Yoshioka, H.: Structure of the human type XIX collagen (COL19A1) gene, which suggests it has arisen from an ancestor gene of the FACIT family. Genomics 45: 304-312, 1997
19) Sumiyoshi, H., Inoguchi, K., Khaleduzzaman, M., Ninomiya, Y. Yoshioka, H.: Ubiquitous expression of the α1(XIX) collagen gene (Col19a1) during mouse embryogenesis becomes restricted to a few tissues in the adult organism. J. Biol. Chem. 272: 17104-17111, 1997
20) Inoguchi, K., Yoshioka, H., Khaleduzzaman, M., Ninomiya, Y.: The mRNA for α1(XIX) collagen chain, a new member of FACITs, contains a long unusual 3' untranslated region and displays many unique splicing variants. J. Biochem. 117: 137-146, 1995
21) Yoshioka, H., Greenwel, P., Inoguchi, K., Truter, S., Inagaki, Y., Ninomiya, Y., Ramirez, F.: Structural and fanctional analysis of the promoter of the human α1(XI) collagen gene. J. Biol. Chem. 270: 418-424, 1995
22) Li, Y., Lacerda, D.A., Warman, M.L., Beier, D.R., Yoshioka, H., Ninomiya, Y., Oxford, J.T., Morris, N.P., Andrikopoulos, K., Ramirez, F., Wardell, B.B., Lifferth, G.D., Teuscher, C., Woodward, S.R., Taylor, B.A., Seegmiller, R.E., Olsen, B.R.: A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis. Cell 80: 423-430, 1995
23) Yoshioka, H., Iyama , K., Inoguchi, K., Khaleduzzaman, M., Ninomiya Y., Ramirez F.: Developmental pattern of expression of the mouse α1(XI) collagen gene (Col11a1). Dev. Dyn. 204: 41-47, 1995
24) Yoshioka, H., Zhang, H., Ramirez, F, Mattei, M.-G., Moradi-Ameli, M., van der Rest M., Gordon, M.K.: Synteny between the loci for a novel FACIT-like collagen locus (D6S228E) and α1(IX) collagen (COL9A1) on 6q12-q14 humans. Genomics 13: 884-886, 1992
25) Yoshioka, H., Ramirez, R.: Pro-α1(XI) collagen : Structure of the amino-terminal propeptide and expression of the gene in tumor cell lines. J. Biol. Chem. 265: 6423-6426, 1990
26) Ramirez F, Boast S, D'Alessio M, Lee B, Prince J, Su MW, Vissing H, Yoshioka H: Fibrillar collagen genes. Structure and expression in normal and diseased states. Ann N Y Acad Sci. 580, 74-80, 1990.
27) Bernard, M., Yoshioka, H., Rodriguez, E., van der Rest, M., Kimura, T., Ninomiya, Y., Olsen, B.R., Ramirez, F.: Cloning and sequencing of pro-α1(XI) collagen cDNA demonstrates that type XI belongs to the fibrillar class of collagens and reveals that the expression of the gene is not restricted to cartilagenous tissue. J. Biol. Chem. 263: 17159-17166, 1988
28) Oyamada I, Kitaoka M, Araki C, Yoshioka H, Usuku G: Collagenase from the culture medium of rabbit colon wall with special reference to the latent type and substrate specificity. Gastroenterology 85, 376-384, 1983.