基本情報
- 所属
- 日本獣医生命科学大学 獣医学部 獣医保健看護学科
- 学位
- 獣医学博士(1989年3月 日本獣医畜産大学)
- 通称等の別名
- 袴田陽二
- J-GLOBAL ID
- 200901087420386440
- researchmap会員ID
- 1000063736
研究キーワード
4経歴
3-
2020年4月 - 現在
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2012年1月 - 現在
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2006年4月 - 2012年1月
論文
69-
Scientific reports 14(1) 26604-26604 2024年11月4日 査読有りGenetic backgrounds of patients with pulmonary arterial hypertension (PAH) were not fully investigated. A variant of c.14429G > A (p.Arg4810Lys) in the ring finger protein 213 gene (RNF213) was recently identified as a risk allele for poor treatment response and poor clinical prognosis in patients with PAH. However, the molecular mechanisms of the RNF213 p.Arg4810Lys variant in development of PAH are unknown. We investigated the underlying molecular mechanisms of RNF213-associated vasculopathy using an in vivo mouse model. RNF213+/p.Arg4828Lys mice, harboring the heterozygous RNF213 p.Arg4828Lys variant corresponding to the p.Arg4810Lys variant in humans, were created using the CRISPR-Cas9 system to recapitulate the genetic status of PAH patients. RNF213+/p.Arg4828Lys mice had a significant elevation of the right ventricular systolic pressure, hypertrophy of the right ventricle, and increased thickness of the pulmonary arterial medial wall compared with wild-type mice after 3 months of exposure to a hypoxic environment. C-X-C motif chemokine ligand 12 (CXCL12), a C-X-C chemokine receptor type 4 (CXCR4) ligand, was significantly elevated in the lungs of RNF213+/p.Arg4828Lys mice, and PAH was ameliorated by the administration of a CXCR4 antagonist. CXCL12-CXCR4 is an angiogenic chemokine axis, and immunohistochemistry demonstrated an increase in CXCR4 in vimentin-positive spindle-shaped cells in adventitia and interstitial lesions in RNF213+/p.Arg4828Lys mice and lung specimens from severe PAH patients with the RNF213 p.Arg4810Lys variant. We confirmed a cause-and-effect relationship between the RNF213 p.Arg4810Lys variant and PAH via the CXCL12-CXCR4 pathway. The findings in this study suggest that targeting this pathway might be a novel therapeutic strategy for RNF213-associated vasculopathy.
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Nanomaterials 14(17) 1440-1440 2024年9月3日 査読有りHemozoin (Hz) is a heme crystal produced during malaria infection that stimulates immune cells, leading to the production of cytokines and chemokines. The immunostimulatory action of Hz has previously been applied in the development of alternative adjuvants. Crystallization of hemin is a chemical approach for producing Hz. Here, we focused on an enzymatic production method for Hz using the heme detoxification protein (HDP), which catalyzes heme dimer formation from hemin in Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading to the production of interleukin (IL)-6 and IL-12p40. In mice, subcutaneous administration of esHz together with an antigen, ovalbumin (OVA), increased the OVA-specific immunoglobulin (Ig) G2c isotype level in the serum, whereas OVA-specific IgG1 was not induced. Our findings suggest that esHz is a useful Th-1 cell adjuvant.
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Impact of daily administration of blackberry extract on gerbil model of transient cerebral ischemia.Acta cirurgica brasileira 39 e397424 2024年 査読有りPURPOSE: Blackberries are rich in polyphenols and are a human health food continuously consumed to improve health and reduce diseases caused by aging. Herein, we evaluated the effects of daily blackberry administration before and after transient cerebral ischemia in gerbils. METHODS: Blackberry extract (BBE) was orally administered twice a day for two weeks to protect against ischemic events during continuous administration. On the seventh day after administration, the bilateral common carotid arteries were transiently occluded for 5 min. To verify its therapeutic effect, BBE was administered after ischemia using a similar protocol without pre-administration. In both experiments, the number of viable neurons in the CA1 region of the hippocampus was assessed seven days after ischemic treatment. RESULTS: The number of neurons in the group treated with BBE before ischemia was higher than that in the group treated with distilled water (p = 0.0601), and similar to that in the control group. In the BBE administration experiments after ischemia, the number of neurons was significantly reduced compared to that in the control group (p < 0.0001). CONCLUSIONS: Continuous BBE intake is expected to prevent or ameliorate ischemic events such as transient cerebral ischemia.
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Acta Cirúrgica Brasileira 39 2024年 査読有り
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Cell transplantation 33 9636897231224174-9636897231224174 2024年 査読有りFireflies produce light through luciferase-catalyzed reactions involving luciferin, oxygen, and adenosine triphosphate, distinct from other luminescent organisms. This unique feature has revolutionized molecular biology and physiology, serving as a valuable tool for cellular research. Luciferase-based bioluminescent imaging enabled the creation of transgenic animals, such as Firefly Rats. Firefly Rats, created in 2006, ubiquitously express luciferase and have become a critical asset in scientific investigations. These rats have significantly contributed to transplantation and tissue engineering studies. Their low immunogenicity reduces graft rejection risk, making them ideal for long-term tracking of organ/tissue/cellular engraftments. Importantly, in the islet transplantation setting, the ubiquitous luciferase expression in these rats does not alter islet morphology or function, ensuring accurate assessments of engrafted islets. Firefly Rats have illuminated the path of transplantation research worldwide for over a decade and continue accelerating scientific advancements in many fields.
MISC
145書籍等出版物
7-
Maturation Phenomenon in Cerebrak Ischemia (]G0004[). 2001年
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Ischemic Blood Flow in the Brain. 2001年
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Maturation Phenomenon in Cerebral Ischemia (]G0003[) 1999年
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Maturation Phenomenon in Cerebral Ischemia (]G0003[) 1999年
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Maturation Phemonenon in Cerebral Ischemia (]G0003[) 1999年
講演・口頭発表等
16Works(作品等)
2共同研究・競争的資金等の研究課題
10-
日本学術振興会 科学研究費助成事業 基盤研究(B) 2020年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2012年4月 - 2015年3月
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文部省 科研費 一般研究(C) 2012年4月 - 2014年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2004年 - 2005年
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2002年 - 2003年
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日本学術振興会 科学研究費助成事業 基盤研究(B) 2001年 - 2003年
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日本学術振興会 科学研究費助成事業 基盤研究(C) 1998年 - 2000年