Regulation of inflammation by stress proteins

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790077
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Keio University (2013); Kumamoto University (2012)
• Principal Investigator: TANAKA Kenichiro 慶應義塾大学, 薬学部, 助教 (30555777)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ストレスタンパク質

Research Abstract

In this study, we have examined the role of HSP70 in gastric ulcer healing. Gastric ulcers were produced by focal and serosal application of acetic acid. Expression of HSP70 was induced in both the gastric ulcer margin and granulation tissue. Compared with wild-type mice, gastric ulcer healing was accelerated in transgenic mice expressing HSP70, and both cell proliferation at the gastric ulcer margin and angiogenesis in granulation tissue were enhanced. Oral administration of geranylgeranylacetone, an inducer of HSPs, to wild-type mice, either prior to or after ulcer formation, not only induced expression of HSP70 in the stomach but also accelerated gastric ulcer healing. On the other hand, oral administration of purified recombinant HSP70 prior to the ulcer formation, but not after formation, stimulated gastric ulcer healing. This study provides the first evidence that HSP70 accelerates gastric ulcer healing.

Research Products

• [Journal Article] Superiority of pulmonary administration of mepenzolate bromide over other routes as treatment for chronic obstructive pulmonary disease (2014)
  • Author(s): Tanaka, K., Kurotsu, S., Asano, T., Yamakawa, N., Kobayashi D., Yamashita, Y., Yamazaki, H., Ishihara, T., Watanabe, H., Maruyama, T., Suzuki, H. and Mizushima, T
  • Journal Title: Sci. Rep Volume: 28 Pages: 4510
• [Journal Article] Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease (2013)
  • Author(s): Tanaka, K., Ishihara, T., Sugizaki, T., Kobayashi D., Yamashita, Y., Tahara, K., Yamakawa, N., Iijima, K., Mogushi, K., Tanaka, H., Sato, K., Suzuki, H. and Mizushima, T
  • Journal Title: Nature Communications Volume: 4 Pages: 2686
• [Journal Article] Long-acting human serum albumin-thioredoxin fusion protein suppresses bleomycin-induced pulmonary fibrosis progression (2013)
  • Author(s): Tanaka, R., Watanabe, H., Kodama, A., Chuang, VTG., Ishima, Y., Hamasaki, K., Tanaka, K, Mizushima, T., Otagiri, M. and Maruyama, T
  • Journal Title: J. Pharmacol. Exp. Ther Volume: 345 Pages: 271-283
  • DOI: 10.1124/jpet.112.201814
• [Journal Article] Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen (2013)
  • Author(s): Yamakawa, N., Suemasu, S., Watanabe, H., Tahara, K., Tanaka, K., Okamoto, Y., Ohtsuka, M., Maruyama, T. and Mizushima, T
  • Journal Title: Drug Metab. Pharmacokinet Volume: 28 Pages: 118-124
• [Journal Article] Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and dysfunction in mice (2012)
  • Author(s): Tanaka, K., Shirai, A., Ito, Y., Namba, T., Tahara, K., Yamakawa, N. and Mizushima, T
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 425 Pages: 818-824
  • DOI: 10.1016/j.bbrc.2012.07.158
• [Journal Article] Identification of a unique NSAID, fluoro-loxoprofen with gastroprotective activity (2012)
  • Author(s): Suemasu, S., Yamakawa, N., Ishihara, T., Asano, T. Tahara, K., Tanaka, K., Matsui, M., Okamoto, Y., Otsuka, M., Takeuchi, K., Suzuki, S. and Mizushima, T
  • Journal Title: Biochem. Pharmacol Volume: 84 Pages: 1470-1481
  • DOI: 10.1016/j.bcp.2012.09.016
• [Journal Article] Effects of lecithinized superoxide dismutase and/or pirfenidone against bleomycin-induced pulmonary fibrosis (2012)
  • Author(s): Tanaka, K., Azuma, A., Miyazaki, Y., Sato, K. and Mizushima, T
  • Journal Title: Chest Volume: 142 Pages: 1011-1019
• [Journal Article] Synthesis and biological evaluation of derivatives of 2-{2-fluoro-4-[(2-oxocyclopentyl)methyl ]phenyl}propanoic acid : Non-steroidal anti-inflammatory drugs with low gastric ulcerogenic activity (2012)
  • Author(s): Yamakawa, N., Suemasu, S., Okamoto, Y., Tanaka, K., Ishihara, T., Asano, T., Miyata, k., Ohtsuka, M. and Mizushima, T
  • Journal Title: J. Med. Chem Volume: 55 Pages: 5143-5150
  • DOI: 10.1021/jm300049g2012
• [Journal Article] Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice (2012)
  • Author(s): Tanaka, K., Sato, K., Aoshiba, K., Azuma, A. and Mizushima, T
  • Journal Title: Am J. Physiol. Lung Cell. Mol. Physiol Volume: 302 Pages: L1250-L1261
  • DOI: 10.1152/ajplung.00019.2012
• [Journal Article] Effects ofβ-(1,3-1,6)-D-glucan on irritable bowel syndrome-related colonic hypersensitivity (2012)
  • Author(s): Asano, T., Tanaka, K. Suemasu, S., Ishihara, T., Tahara, K., Suzuki, T., Suzuki, H., Fukudo, S. and Mizushima, T
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 420 Pages: 444-449
  • DOI: 10.1016/j.bbrc.2012.03.015
• [Journal Article] Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities
  • Author(s): Yamashita, Y., Tanaka, K., Asano, T., Yamakawa, N., Kobayashi D., Ishihara, T., Hanaya, K., Shoji, M., Sugai, T., Wada, M., Mashimo, T., Fukunishi, Y. and Mizushima T
  • Journal Title: Bioorg. & Medic. Chem Volume: (in press)
• [Journal Article] Ameliorative effect of mepenzolate bromide against pulmonary fibrosis
  • Author(s): Kurotsu, S., Tanaka, K., Niino, T., Sugizaki, T., Azuma, A., Suzuki, H. and Mizushima, T
  • Journal Title: J. Pharmacol. Exp. Ther Volume: (in press)