Ryota Tanaka

Publications (3)16.16 Total impact

• Article: Long-acting human serum albumin-thioredoxin fusion protein suppresses bleomycin-induced pulmonary fibrosis progression.

  Ryota Tanaka, Hiroshi Watanabe, Azusa Kodama, Victor Tuan Giam Chuang, Yu Ishima, Keisuke Hamasaki, Ken-Ichiro Tanaka, Tohru Mizushima, Masaki Otagiri, Toru Maruyama
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  ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory cells and reactive oxygen species (ROS), such as superoxide anion radical (O(2)(·-)). There is currently no effective treatment for IPF. We previously developed a human serum albumin (HSA)-thioredoxin 1 (Trx) fusion protein (HSA-Trx), designed to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx, an anti-oxidative and anti-inflammatory protein. In this study, we examined the therapeutic effect of HSA-Trx on an IPF animal model of bleomycin (BLM)-induced pulmonary fibrosis. A pharmacokinetic study of HSA-Trx or Trx in BLM mice showed that the plasma retention and lung distribution of Trx was markedly improved by fusion with HSA. A weekly intravenous administration of HSA-Trx, but not Trx, ameliorated BLM-induced fibrosis as evidenced by a histopathological analysis and pulmonary hydroxyproline levels. HSA-Trx suppressed active-TGF-β levels in the lung and inhibited the increase of inflammatory cells in BALF, pulmonary inflammatory cytokines and oxidative stress markers. An in vitro EPR experiment using PMA-stimulated neutrophils confirmed the O(2)(·-) scavenging ability of HSA-Trx. Furthermore, post-treatment of HSA-Trx had a suppressive effect against BLM-induced fibrosis. These results suggest that HSA-Trx has potential as a novel therapeutic agent for IPF, due to its long-acting anti-oxidative and anti-inflammatory modulation effects.
  Journal of Pharmacology and Experimental Therapeutics 02/2013; · 3.83 Impact Factor
• Article: A human serum albumin-thioredoxin fusion protein prevents experimental contrast-induced nephropathy.

  Azusa Kodama, Hiroshi Watanabe, Ryota Tanaka, Hisae Tanaka, Victor T G Chuang, Yohei Miyamoto, Qiong Wu, Masayuki Endo, Keisuke Hamasaki, Yu Ishima, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
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  ABSTRACT: Contrast-induced nephropathy (CIN), caused by a combination of the direct tubular toxicity of contrast media, a reduction in medullary blood flow, and the generation of reactive oxygen species, is a serious clinical problem. A need exists for effective strategies for its prevention. Thioredoxin-1 (Trx) is a low-molecular-weight endogenous redox-active protein with a short half-life in the blood due to renal excretion. We produced a long-acting form of Trx as a recombinant human albumin-Trx fusion protein (HSA-Trx) and examined its effectiveness in preventing renal injury in a rat model of ioversol-induced CIN. Compared with saline, a mixture of HSA and Trx, or Trx alone, intravenous HSA-Trx pretreatment significantly attenuated elevations in serum creatinine, blood urea nitrogen, and urinary N-acetyl-β-D-glucosaminidase along with the decrease in creatinine clearance. HSA-Trx also caused a substantial reduction in the histological features of renal tubular injuries and in the number of apoptosis-positive tubular cells. Changes in the markers 8-hydroxy deoxyguanosine and malondialdehyde indicated that HSA-Trx significantly suppressed renal oxidative stress. In HK-2 cells, HSA-Trx decreased the level of reactive oxygen species induced by hydrogen peroxide, and subsequently improved cell viability. Thus, our results suggest that due to its long-acting properties, HSA-Trx has the potential to effectively prevent CIN.Kidney International advance online publication, 2 January 2013; doi:10.1038/ki.2012.429.
  Kidney International 01/2013; · 6.61 Impact Factor
• Article: Human serum albumin-thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury.

  Masato Furukawa, Ryota Tanaka, Victor Tuan Giam Chuang, Yu Ishima, Kazuaki Taguchi, Hiroshi Watanabe, Toru Maruyama, Masaki Otagiri
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  ABSTRACT: Thioredoxin (Trx) is a redox-active protein with anti-inflammatory effects but with a short half life of 1 h. Genetic fusion of Trx to human serum albumin (HSA) extended its half life without causing significant loss of its biological activities. HSA-Trx caused a decrease in the number of cells in brochoalveolar lavage fluid, the wet/dry ratio and the inflammation at the respiratory tract of the ovalbumin (OVA) induced lung injury model mouse. Three intraperitoneal doses of Trx alone produced the same extent of suppression of those three detrimental effects of OVA as one intravenous dose of HSA-Trx. Inhibition experiments confirmed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) involved in the progression of the injury. HSA-Trx inhibited the production of ROS as confirmed in the EPR experiment, but lung tissue staining suggested that induced nitrogen oxide synthase (iNOS) was not suppressed by the fusion protein. Instead, the production of nitrotyrosine, 8-nitro-cGMP, and 8-hydroxy-2'-deoxyguanosine downstream to the iNOS has been inhibited. This suggested that HSA-Trx produced lung protection effect via different mechanisms from Trx alone. HSA-Trx retains the biological properties of Trx thus has great potential in treating oxidative stress related diseases.
  Journal of Controlled Release 05/2011; 154(2):189-95. · 5.73 Impact Factor