担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.celrep.2017.10.075

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/srep29945

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1750-1326-7-48

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nature11333

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1126/science.1140481

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.biopsych.2013.10.027

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1074/jbc.M607290200

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PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING LTD  

CIZ (Cas interacting zinc finger protein), also called Nmp4 (nuclear matrix protein 4), is a nucleocytoplasmic shuttling transcription factor that regulates the expression of collagen and matrix metalloproteinases. CIZ/Nmp4 was originally cloned by its binding to p130(Cas), a focal adhesion protein, and was recently shown to suppress BMP2 (bone mophogenetic protein 2) signalling. To explore the physiological role of CIZ/Nmp4, we disrupted CIZ/Nmp4-gene by inserting beta-galactosidase and neomycin resistance genes into the 2nd exon of CIZ/Nmp4-gene, which is utilized by all the sequenced alternative forms. CIZ(-/-) mice were born and grew to adulthood. Although they tend to be smaller than wild-type mice, no pathological abnormality was observed except in the testis. Histological analysis of the testes revealed variable degrees of spermatogenic cell degeneration within the seminiferous tubules of CIZ(-/-) mice, resembling the histology of the 'Germinal-cell aplasia with focal spermatogenesis'. Some of the CIZ(-/-) male mice developed infertility. TUNEL assay on testis sections revealed an increased occurrence of apoptosis of spermatogenic cells in the testes of CIZ(-/-) mice. CIZ/Nmp4 was co-localized with Smad1 in the testis, suggesting that a disregulation of BMP signalling could cause these phenotypes. These results suggest that CIZ/Nmp4 plays roles in the progress and the maintenance of spermatogenesis.

DOI： 10.1111/j.1365-2443.2004.00746.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Previous studies have reported a neuroprotective role for cellular prion protein (PrPC) against apoptosis induced by serum deprivation in an immortalized prion protein gene (Prnp)-deficient neuronal cell line, but the mechanisms remain unclear. In this study, to investigate the mechanisms by which PrPC prevents apoptosis, the authors compared apoptosis of Prnp(-/-) cells with that of Prnp(-/-) cells expressing the wild-type PrPC or PrPC lacking N-terminal octapeptide repeat region under serum-free conditions. Re-introduction of Prnp rescued cells from apoptosis, upregulated superoxide dismutase (SOD) activity, enhanced superoxide anion elimination, and inhibited caspase-3/9 activation. On the other hand, N-terminally truncated PrPC enhanced apoptosis accompanied by potentiation of superoxide production and caspase-3/9 activation due to inhibition of SOD. These results suggest that PrPC protects Prnp(-/-) cells from apoptosis via superoxide- and caspase-3/9-dependent pathways by upregulating SOD activity. Furthermore, the octapeptide repeat region of PrPC plays an essential role in regulating apoptosis and SOD activity. (C) 2003 Elsevier Inc. All rights reserved.

DOI： 10.1016/S0006-29IX(03)01459-1

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：SPRINGER-VERLAG WIEN  

The physiological function of the normal cellular form of prion protein (PrPC) is not yet fully understood. In the current study we used prion protein gene knock-out mice (Prnp(-/-)) to assess the role of PrPC in traumatic brain injury. Prnp(+/-) and Prnp(-/-) mice were subjected to weight-drop contusional brain injury over the left parietal cortex. Prnp(-/-) mice manifested a significantly larger lesion volume and worse neuromotor scores than did their Prnp(+/-) litter-mates. IgG immunostaining revealed that in Prnp(-/-) mice the breakdown in the blood-brain barrier (BBB) was more extensive at 1 month after brain injury. Our results are in agreement with previous in vitro findings of the neuroprotective role of PrPC and further support the hypothesis that functional loss of PrPc plays a pathogenic role in prion diseases. We also suggest that PrPc modulates BBB function.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

Glioma, the most common form of brain tumor, has been shown mostly by in vitro studies to utilize matrix metalloproteinase (MMP) for invasive growth through degradation of the extracellular matrix. In order to examine the in vivo role of MMP, we established a rodent model of glioma progression using C6 rat glioma cells and analyzed the effect of tissue inhibitors of metalloproteinases (TIMPs). TIMP-2 rather than TIMP-1 caused significant reduction of the tumor size accompanied by the presence of degenerated blood vessels and ischemic necrosis. Because TIMP-2 inhibits MMP-2 preferentially, we then examined glioma growth in MMP-2-deficient mice and observed essentially identical consequences. While MMP-2 activity was present in the tumor and adjacent tissues of the wild-type mice, no MMP-2 activity was detected even in the tumor of the null mice, although C6 cells are known to express MMP-2. These observations suggest that glioma induces MMP-2 and utilizes its activity in the host tissue to support angiogenesis and to maintain angioarchitecture. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S1043-6618(02)00081-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Transmissible spongiform encephalopathies are characterized by the accumulation of a proteinase-resistant isoform of the cellular prion-related protein (PrPe) within the central nervous system (CNS), The accumulation of scrapie-associated PrP (PrPSc) within cells of the lymphoreticular system prior to its accumulation in the CNS is regarded as important for the development of neurological diseases after peripheral inoculation. Little, however, is known as to which cells are the targets for peripheral inoculation. Here. the presence of PrPe on murine Langerhans cells (LC), dendritic cells in the skin and mucosa. and keratinocytes (KC) is demonstrated by immunohistochemical staining, Western-blotting and FACS analysis. The expression of PrPc mRNA in freshly purified LC and KC was also detected by reverse transcriptase-polymerase chain reaction. The expression of PrPc on LC was slightly increased during culture. These data suggest that LC and KC may be the targets for peripheral infection with prions. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（その他）  

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記述言語：英語   掲載種別：速報，短報，研究ノート等（大学，研究機関紀要）  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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