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| 1.
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論文
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浅野, 雄哉 ; 石丸, 和宏 ; 多久和, 陽 ; Asano, Yuya ; Ishimaru, Kazuhiro ; Takuwa, Yoh
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修士課程優秀論文
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Zhao, Juanjuan ; Okamoto, Yasuo ; Asano, Yuya ; Ishimaru, Kazuhiro ; Aki, Sho ; Yoshioka, Kazuaki ; Takuwa, Noriko ; Wada, Takashi ; Inagaki, Yutaka ; Takahashi, Chiaki ; Nishiuchi, Takumi ; Takuwa, Yoh ; 安藝, 翔 ; 吉岡, 和晃 ; 多久和, 典子 ; 和田, 隆志 ; 髙橋, 智聡 ; 西内, 巧 ; 多久和, 陽
概要:
金沢大学医薬保健研究域医学系<br />Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of t
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he lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2 LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions. Bone marrow chimera experiments suggested that S1PR2 in bone marrow–derived cells contributes to the development of lung fibrosis. Depletion of macrophages greatly attenuated lung fibrosis. Bleomycin administration stimulated the mRNA expression of the profibrotic cytokines IL-13 and IL-4 and the M2 markers including arginase 1, Fizz1/Retnla, Ccl17 and Ccl24 in cells collected from broncho-alveolar lavage fluids (BALF), and S1pr2 deletion markedly diminished the stimulated expression of these genes. BALF cells from bleomycin–administered wild-type mice showed a marked increase in phosphorylation of STAT6, a transcription factor which is activated downstream of IL-13, compared with saline–administered wild-type mice. Interestingly, in bleomycin–adminis-tered S1pr2 -/- mice, STAT6 phosphorylation in BALF cells was substantially diminished compared with wild-type mice. Finally, pharmacological S1PR2 blockade in S1pr2 +/+ mice alleviated bleomycin–induced lung fibrosis. Thus, S1PR2 facilitates lung fibrosis through the mechanisms involving augmentation of IL-13 expression and its signaling in BALF cells, and represents a novel target for treating lung fibrosis. © 2018 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 3.
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Pham, Hoa Q. ; Yoshioka, Kazuaki ; Mohri, Hiromi ; Nakata, Hiroki ; Aki, Sho ; Ishimaru, Kazuhiro ; Takuwa, Noriko ; Takuwa, Yoh ; 吉岡, 和晃 ; 仲田, 浩規 ; 安藝, 翔 ; 多久和, 典子 ; 多久和, 陽
概要:
金沢大学医薬保健研究域医学系<br />Phosphatidylinositol 3-phosphate (PI(3)P) is the predominant phosphoinositide species in early endos
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omes and autophagosomes, in which PI(3)P dictates traffic of these organelles. Phosphoinositide levels are tightly regulated by lipid-kinases and -phosphatases; however, a phosphatase that converts PI(3)P back to phosphatidylinositol in the endosomal and autophagosomal compartments is not fully understood. We investigated the subcellular distribution and functions of myotubularin-related protein-4 (MTMR4), which is distinct among other MTMRs in that it possesses a PI(3)P-binding FYVE domain, in lung alveolar epithelium-derived A549 cells. MTMR4 was localized mainly in late endosomes and autophagosomes. MTMR4 knockdown markedly suppressed the motility, fusion, and fission of PI(3)P-enriched structures, resulting in decreases in late endosomes, autophagosomes, and lysosomes, and enlargement of PI(3)P-enriched early and late endosomes. In amino acid- and serum-starved cells, MTMR4 knockdown decreased both autophagosomes and autolysosomes and markedly increased PI(3)P-containing autophagosomes and late endosomes, suggesting that the fusion with lysosomes of autophagosomes and late endosomes might be impaired. Notably, MTMR4 knockdown inhibited the nuclear translocation of starvation stress responsive transcription factor-EB (TFEB) with reduced expression of lysosome-related genes in starved cells. These findings indicate that MTMR4 is essential for the integrity of endocytic and autophagic pathways. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.<br />Embargo Period 12 months
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| 4.
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論文
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Aung, Khin Thuzar ; Yoshioka, Kazuaki ; Aki, Sho ; Ishimaru, Kazuhiro ; Takuwa, Noriko ; Takuwa, Yoh ; 吉岡, 和晃 ; 安藝, 翔 ; 多久和, 典子 ; 多久和, 陽
概要:
金沢大学医薬保健研究域医学系<br />Pinocytosis is an important fundamental cellular process that is used by the cell to transport fluid
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and solutes. Phosphoinositide 3-kinases (PI3Ks) regulate a diverse array of dynamic membrane events. However, it is not well-understood which PI3K isoforms are involved in specific mechanisms of pinocytosis. We performed knockdown studies of endogenous PI3K isoforms and clathrin heavy chain (CHC) mediated by small interfering RNA (siRNA). The results demonstrated that the class II PI3K PI3K-C2α and PI3K-C2β, but not the class I or III PI3K, were required for pinocytosis, based on an evaluation of fluorescein-5-isothiocyanate (FITC)–dextran uptake in endothelial cells. Pinocytosis was partially dependent on both clathrin and dynamin, and both PI3K-C2α and PI3K-C2β were required for clathrin-mediated—but not clathrin-non-mediated—FITC-dextran uptake at the step leading up to its delivery to early endosomes. Both PI3K-C2α and PI3K-C2β were co-localized with clathrin-coated pits and vesicles. However, PI3K-C2β, but not PI3K-C2α, was highly co-localized with actin filament-associated clathrin-coated structures and required for actin filament formation at the clathrin-coated structures. These results indicate that PI3K-C2α and PI3K-C2β play differential, indispensable roles in clathrin-mediated pinocytosis. © 2018, The Physiological Society of Japan and Springer Japan KK, part of Springer Nature.<br />Embargo Period 12 months
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| 5.
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論文
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Sarker, Md Azadul Kabir ; Aki, Sho ; Yoshioka, Kazuaki ; Kuno, Kouji ; Okamoto, Yasuo ; Ishimaru, Kazuhiro ; Takuwa, Noriko ; Takuwa, Yoh ; 安藝, 翔 ; 吉岡, 和晃 ; 多久和, 典子 ; 多久和, 陽
概要:
金沢大学医薬保健研究域医学系<br />Class II phosphoinositide 3-kinases (PI3Ks), PI3K-C2α and PI3K-C2β, are highly homologous and distin
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ct from class I and class III PI3Ks in catalytic products and domain structures. In contrast to class I and class III PI3Ks, physiological roles of PI3K-C2α and PI3K-C2β are not fully understood. Because we previously demonstrated that PI3K-C2α is involved in vascular smooth muscle contraction, we studied the phenotypes of smooth muscle-specific knockout (KO) mice of PI3K-C2α and PI3K-C2β. The pup numbers born from single PI3K-C2α-KO and single PI3K-C2β-KO mothers were similar to those of control mothers, but those from double KO (DKO) mothers were smaller compared with control mice. However, the number of intrauterine fetuses in pregnant DKO mothers was similar to that in control mice. Both spontaneous and oxytocin-induced contraction of isolated uterine smooth muscle (USM) strips was diminished in DKO mice but not in either of the single KO mice, compared with control mice. Furthermore, contraction of USM of DKO mice was less sensitive to a Rho kinase inhibitor. Mechanistically, the extent of oxytocin-induced myosin light chain phosphorylation was greatly reduced in USM from DKO mice compared with control mice. The oxytocin-induced rise in the intracellular Ca2+ concentration in USM was similar in DKO and control mice. However, Rho activation in the intracellular compartment was substantially attenuated in DKO mice compared with control mice, as evaluated by fluorescence resonance energy transfer imaging technique. These data indicate that both PI3K-C2α and PI3K-C2β are required for normal USM contraction and parturition mainly through their involvement in Rho activation.<br />Embargo Period 12 months
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金沢大学フロンティアサイエンス機構 ; 長谷川, 浩 ; 桑原, 貴之 ; 児玉, 昭雄 ; 徳田, 規夫 ; 田中, 康規 ; 中村, 裕之 ; 井上, 啓 ; 堀, 修 ; 平尾, 敦 ; 横井, 毅 ; 土屋, 弘行 ; 宮地, 利明 ; 多久和, 陽 ; 白土, 明子 ; Hasegawa, Hiroshi ; Kuwabara, Takayuki ; Kodama, Akio ; Tokuda, Norio ; Tanaka, Yasunori ; Nakamura, Hiroyuki ; Inoue, Hiroshi ; Hori, Osamu ; Hirao, Atsushi ; Yokoi, Tsuyoshi ; Tsuchiya, Hiroyuki ; Miyachi, Toshiaki ; Takuwa, Yoh ; Shiratsuchi, Akiko
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王, 飛 ; 岡本, 安雄 ; 多久和, 陽
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[総説][Reviews] 第9回高安賞最優秀賞受賞論文, [博士課程優秀論文] , Journal of Clinical Invetigatin, 120(1), pp.3979-3995(Nov. 2011)
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杜, 娃 ; 多久和, 陽
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[博士課程優秀論文]第8回高安賞最優秀賞受賞論文
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| 9.
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吉岡, 和晃 ; 多久和, 陽
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[総説]
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| 10.
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多久和, 陽
概要:
学会開催報告 / Reviews
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