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排序方式: 共有504条查询结果,搜索用时 15 毫秒
81.
82.
Onozuka I Kakinuma S Kamiya A Miyoshi M Sakamoto N Kiyohashi K Watanabe T Funaoka Y Ueyama M Nakagawa M Koshikawa N Seiki M Nakauchi H Watanabe M 《Biochemical and biophysical research communications》2011,406(1):134-140
Matrix metalloproteinase (MMP) plays an important role in homeostatic regulation of the extracellular environment and degradation of matrix. During liver fibrosis, several MMPs, including MMP-2, are up-regulated in activated hepatic stellate cells, which are responsible for exacerbation of liver cirrhosis. However, it remains unclear how loss of MMP-2 influences molecular dynamics associated with fibrogenesis in the liver. To explore the role of MMP-2 in hepatic fibrogenesis, we employed two fibrosis models in mice; toxin (carbon tetrachloride, CCl4)-induced and cholestasis-induced fibrosis. In the chronic CCl4 administration model, MMP-2 deficient mice exhibited extensive liver fibrosis as compared with wild-type mice. Several molecules related to activation of hepatic stellate cells were up-regulated in MMP-2 deficient liver, suggesting that myofibroblastic change of hepatic stellate cells was promoted in MMP-2 deficient liver. In the cholestasis model, fibrosis in MMP-2 deficient liver was also accelerated as compared with wild type liver. Production of tissue inhibitor of metalloproteinase 1 increased in MMP-2 deficient liver in both models, while transforming growth factor β, platelet-derived growth factor receptor and MMP-14 were up-regulated only in the CCl4 model. Our study demonstrated, using 2 experimental murine models, that loss of MMP-2 exacerbates liver fibrosis, and suggested that MMP-2 suppresses tissue inhibitor of metalloproteinase 1 up-regulation during liver fibrosis. 相似文献
83.
84.
Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche 总被引:2,自引:0,他引:2
Yamazaki S Ema H Karlsson G Yamaguchi T Miyoshi H Shioda S Taketo MM Karlsson S Iwama A Nakauchi H 《Cell》2011,147(5):1146-1158
Hematopoietic stem cells (HSCs) reside and self-renew in the bone marrow (BM) niche. Overall, the signaling that regulates stem cell dormancy in the HSC niche remains controversial. Here, we demonstrate that TGF-β type II receptor-deficient HSCs show low-level Smad activation and impaired long-term repopulating activity, underlining the critical role of TGF-β/Smad signaling in HSC maintenance. TGF-β is produced as a latent form by a variety of cells, so we searched for those that express activator molecules for latent TGF-β. Nonmyelinating Schwann cells in BM proved responsible for activation. These glial cells ensheathed autonomic nerves, expressed HSC niche factor genes, and were in contact with a substantial proportion of HSCs. Autonomic nerve denervation reduced the number of these active TGF-β-producing cells and led to rapid loss of HSCs from BM. We propose that glial cells are components of a BM niche and maintain HSC hibernation by regulating activation of latent TGF-β. 相似文献
85.
Sawayama M Suzuki T Hashimoto H Kasai T Furutani M Miyata N Kunoh H Takada J 《Current microbiology》2011,63(2):173-180
Leptothrix species in aquatic environments produce uniquely shaped hollow microtubules composed of aquatic inorganic and bacterium-derived
organic hybrids. Our group termed this biologically derived iron oxide as “biogenous iron oxide (BIOX)”. The artificial synthesis
of most industrial iron oxides requires massive energy and is costly while BIOX from natural environments is energy and cost
effective. The BIOX microtubules could potentially be used as novel industrial functional resources for catalysts, adsorbents
and pigments, among others if effective and efficient applications are developed. For these purposes, a reproducible system
to regulate bacteria and their BIOX productivity must be established to supply a sufficient amount of BIOX upon industrial
demand. However, the bacterial species and the mechanism of BIOX microtubule formation are currently poorly understood. In
this study, a novel Leptothrix sp. strain designated OUMS1 was successfully isolated from ocherous deposits in groundwater by testing various culture media
and conditions. Morphological and physiological characters and elemental composition were compared with those of the known
strain L. cholodnii SP-6 and the differences between these two strains were shown. The successful isolation of OUMS1 led us to establish a basic
system to accumulate biological knowledge of Leptothrix and to promote the understanding of the mechanism of microtubule formation.
Additional geochemical studies of the OUMS1-related microstructures are expected provide an attractive approach to study the
broad industrial application of bacteria-derived iron oxides. 相似文献
86.
Jayakumar AR Panickar KS Curtis KM Tong XY Moriyama M Norenberg MD 《Journal of neurochemistry》2011,117(3):437-448
Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury (TBI). An important early component of the edema associated with TBI is astrocyte swelling (cytotoxic edema). Mechanisms for such swelling, however, are poorly understood. Ion channels/transporters/exchangers play a major role in cell volume regulation, and a disturbance in one or more of these systems may result in cell swelling. To examine potential mechanisms in TBI-mediated brain edema, we employed a fluid percussion model of in vitro barotrauma and examined the role of the ion transporter Na(+)-K(+)-2Cl(-)-cotransporter 1 (NKCC1) in trauma-induced astrocyte swelling as this transporter has been strongly implicated in the mechanism of cell swelling in various neurological conditions. Cultures exposed to trauma (3, 4, 5 atm pressure) caused a significant increase in NKCC1 activity (21%, 42%, 110%, respectively) at 3 h. At 5 atm pressure, trauma significantly increased NKCC1 activity at 1 h and it remained increased for up to 3 h. Trauma also increased the phosphorylation (activation) of NKCC1 at 1 and 3 h. Inhibition of MAPKs and oxidative/nitrosative stress diminished the trauma-induced NKCC1 phosphorylation as well as its activity. Bumetanide, an inhibitor of NKCC1, significantly reduced the trauma-induced astrocyte swelling (61%). Silencing NKCC1 with siRNA led to a reduction in trauma-induced NKCC1 activity as well as in cell swelling. These findings demonstrate the critical involvement of NKCC1 in the astrocyte swelling following in vitro trauma, and suggest that blocking NKCC1 activity may represent a useful therapeutic strategy for the cytotoxic brain edema associated with the early phase of TBI. 相似文献
87.
Yuki Kawakami Shiori Hirano Mai Kinoshita Akemi Otsuki Toshiko Suzuki-Yamamoto Makiko Suzuki Masumi Kimoto Sae Sasabe Mitsuo Fukushima Koji Kishimoto Takashi Izumi Toru Oga Shuh Narumiya Mitsuaki Sugahara Masashi Miyano Shozo Yamamoto Yoshitaka Takahashi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Cysteinyl leukotrienes (LTs) are key mediators in inflammation. To explore the structure of the antigen-recognition site of a monoclonal antibody against LTC4 (mAbLTC), we previously isolated full-length cDNAs for heavy and light chains of the antibody and prepared a single-chain antibody comprising variable regions of these two chains (scFvLTC).Methods
We examined whether mAbLTC and scFvLTC neutralized the biological activities of LTC4 and LTD4 by competing their binding to their receptors.Results
mAbLTC and scFvLTC inhibited their binding of LTC4 or LTD4 to CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R) overexpressed in Chinese hamster ovary cells. The induction by LTD4 of monocyte chemoattractant protein-1 and interleukin-8 mRNAs in human monocytic leukemia THP-1 cells expressing CysLT1R was dose-dependently suppressed not only by mAbLTC but also by scFvLTC. LTC4- and LTD4-induced aggregation of mouse platelets expressing CysLT2R was dose-dependently suppressed by either mAbLTC or scFvLTC. Administration of mAbLTC reduced pulmonary eosinophil infiltration and goblet cell hyperplasia observed in a murine model of asthma. Furthermore, mAbLTC bound to CysLT2R antagonists but not to CysLT1R antagonists.Conclusions
These results indicate that mAbLTC and scFvLTC neutralize the biological activities of LTs by competing their binding to CysLT1R and CysLT2R. Furthermore, the binding of cysteinyl LT receptor antagonists to mAbLTC suggests the structural resemblance of the LT-recognition site of the antibody to that of these receptors.General significance
mAbLTC can be used in the treatment of inflammatory diseases such as asthma. 相似文献88.
Tetsuya Ito Yutaka Sendai Satoshi Yamazaki Marie Seki-Soma Kensuke Hirose Motoo Watanabe Kazuo Fukawa Hiromitsu Nakauchi 《PloS one》2014,9(12)
Although severe combined immune deficiency (SCID) is a very important research model for mice and SCID mice are widely used, there are only few reports describing the SCID pig models. Therefore, additional research in this area is needed. In this study, we describe the generation of Recombination activating gene-1 (Rag-1)-deficient neonatal piglets in Duroc breed using somatic cell nuclear transfer (SCNT) with gene targeting and analysis using fluorescence-activated cell sorting (FACS) and histology. We constructed porcine Rag-1 gene targeting vectors for the Exon 2 region and obtained heterozygous/homozygous Rag-1 knockout cell colonies using SCNT. We generated two Rag-1-deficient neonatal piglets and compared them with wild-type neonatal piglets. FACS analysis showed that Rag-1 disruption causes a lack of Immunoglobulin M-positive B cells and CD3-positive T cells in peripheral blood mononuclear cells. Consistent with FACS analysis, histological analysis revealed structural defects and an absence of mature lymphocytes in the spleen, mesenteric lymph node (MLNs), and thymus in Rag-1-deficient piglets. These results confirm that Rag-1 is necessary for the generation of lymphocytes in pigs, and Rag-1-deficient piglets exhibit a T and B cell deficient SCID (T-B-SCID) phenotype similar to that of rodents and humans. The T-B-SCID pigs with Rag-1 deficiency generated in this study could be a suitably versatile model for laboratory, translational, and biomedical research, including the development of a humanized model and assessment of pluripotent stem cells. 相似文献
89.
90.
Junji Sakurada Li Zhijun Keiko Seki Miyo Murai Akemi Usui Mami Morihigashi Hiroko Jitsukawa Hee Kyung Seong Mitsuaki Mutou Shogo Masuda 《FEMS microbiology letters》1994,119(1-2):59-63
Abstract We investigated the biochemical and genetic heterogeneity of protein A from Staphylococcus aureus . SpA genes ( spas ) of various strains were heterogeneous when detected as Dra I and Eco RV fragments of chromosomal DNA. Polymerase chain reaction using primers to detect DNA encoding the IgG-binding domains in spa revealed that they numbered between 2 and 5. Protein A from several S. aureus strains showed two types of reactivities to immunoglobulins in normal canine serum according to the number of active domains. 相似文献