检索结果-内蒙古大学图书馆

AMSC-derived exosomes alleviate lipopolysaccharide/D-galactosamine-induced acute liver failure by miR-17-mediated reduction of txnip/NLRP3 inflammasome activation in macrophages

引用

EBIOMEDICINE 2018年 36卷 140-150页

作者： Liu, Yanning Lou, Guohua Li, Aichun Zhang, Tianbao Qi, Jinjin Ye, Dan Zheng, Min Chen, Zhi Zhejiang Univ Sch Med Affiliated Hosp 1State Key Lab Diag & Treatment Collaborat Innovat Ctr Diag & Treatment Infect Di Hangzhou Zhejiang Peoples R China Zhejiang Univ Sch Med Affiliated Hosp 1 Dept Endocrinol & Metab Hangzhou Zhejiang Peoples R China

Background: Mesenchymal stem cell (MSC)-derived exosome administration has been considered as a novel cell-free therapy for liver diseases through cell-cell communication. This study was aimed to determine the effects and mechanisms of AMSC-derived exosomes (AMSC-Exo) for acute liver failure (ALF) treatment. Methods: AMSC-Exo were intravenously administrated into the mice immediately after lipopolysaccharide and D-galactosamine (LPS/GalN)-exposure and their effects were evaluated by liver histological and scrum biochemical analysis. To elucidate its mechanisms in ALF therapy, the expression levels of miRNAs and inflammasome-related genes in macrophages were evaluated by qPCR and Western blot analysis, respectively. The exosomes from miR-17-knockdowned AMSCs (AMSC-Exo(miR-1-KD)) were used for further determine the role of miR-17 in AMSC-Exo-based therapy. Findings: AMSC-Exo administration significantly ameliorated ALF as determined by reduced serum alanine aminotransferase and aspartate aminotransferase levels and hepatic inflammasome activation. Further experiments revealed that AMSC-Exo were colocalized with hepatic macrophages and could reduce inflammatory factor secretion by suppressing inflammasome activation in macrophages. Moreover, miR-17, which can suppress NLRP3 inflammasome activation by targeting txnip, was abundant in AMSC-Exo cargo. While, the therapeutic effects of AMSC-Exo(miR-1-KD) on ALF were significantly abolished as they could not effectively suppress txnip expression and consequent inflammasome activation in vitro and in vivo. Interpretation: Exosome-shuttled miR-17 plays an essential role in AMSC-Exo therapy for ALF by targeting txnip and suppressing inflammasome activation in hepatic macrophages. AMSC-Exo-based therapy may present as a promising approach for txnip/NLRP3 inflammasome-related inflammatory liver diseases. (C) 2018 The Authors. Published by Elsevier B.V.

关键词： Mesenchymal stem cells Exosome Macrophage miR-17 txnip NLRP3 inflammasome

来源：评论

学校读者我要写书评

暂无评论

txnip/NLRP3炎性小体通路在COPD患者机体炎症反应中的作用研究

引用

中国免疫学杂志 2019年第6期35卷 729-734页

作者：王晓玲黄钟邓广雪何子凡刘冬卢献灵石河子大学医学院第一附属医院石河子832000

目的:探讨txnip/NLRP3炎性小体通路在COPD患者发病机制中的可能作用。方法:选取2017年11月至2018年5月住院的40例COPD患者为急性加重期组,其经过治疗进入稳定期后纳入稳定期组,40例健康体检者为对照组。荧光定量PCR法测定外周血单个核... 详细信息

目的:探讨txnip/NLRP3炎性小体通路在COPD患者发病机制中的可能作用。方法:选取2017年11月至2018年5月住院的40例COPD患者为急性加重期组,其经过治疗进入稳定期后纳入稳定期组,40例健康体检者为对照组。荧光定量PCR法测定外周血单个核细胞中txnip mRNA、NLRP3 mRNA水平,Western blot法检测外周血单个核细胞中txnip及NLRP3蛋白表达水平。结果:(1)COPD患者急性加重期组NLRP3、txnip的mRNA和蛋白表达水平均显著高于对照组(P<0. 05)和稳定期组(P<0. 05); COPD患者稳定期组的NLRP3 mRNA和蛋白表达水平显著高于对照组(P<0. 05)。(2)相关性分析:急性加重期组NLRP3 mRNA表达量与FEV1%pred、FEV1/FVC负相关;急性加重期组和稳定期组的NLRP3 mRNA、txnip mRNA表达量均与CAT评分正相关。结论:txnip/NLRP3炎性小体通路参与COPD患者的机体炎症反应。

关键词： COPD txnip NLRP3炎性小体外周血单个核细胞

来源：评论

学校读者我要写书评

暂无评论

The RPMI-1640 vitamin mixture promotes bovine blastocyst development in vitro and downregulates gene expression of txnip with epigenetic modification of associated histones

引用

JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE 2018年第1期9卷 87-94页

作者： Ikeda, S. Sugimoto, M. Kume, S. Kyoto Univ Grad Sch Agr Lab Anim Physiol & Funct Anat Kyoto 6068502 Japan

Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short-and long-term manner. Thioredoxin-interacting protein (txnip) is a possible marker for preimplantation stress that is implicated in in vitro fertilization- (IVF) induced long-term DOHaD effects. B vitamins, as participants in one-carbon metabolism, may affect preimplantation embryos by epigenetic alterations of metabolically and developmentally important genes. In vitro-produced bovine embryos were cultured with or without Roswell Park Memorial Institute 1640 vitamin mixture, containing B vitamins and B vitamin-like substances, from day 3 after IVF and we evaluated blastocyst development and txnip messenger RNA (mRNA) expression in the blastocysts by reverse transcription-quantitative polymerase chain reaction. The degree of trimethylation of histone H3 lysine 27 (H3K27me3) at txnip promoter was examined semi-quantitatively by chromatin immunoprecipitation polymerase chain reaction. Total H3K27me3 were also compared between the groups by Western blot analysis. The vitamin treatment significantly increased the rates of blastocyst development (P < 0.05) and their hatching (P < 0.001) from the zona pellucida by day 8. The mRNA expression of txnip was lower (P < 0.01) in blastocysts in the vitamin-mixture-treated group concomitant with higher (P < 0.05) level of H3K27me3 of its promoter compared with the control group. The total H3K27me3 in the vitamin-mixture-treated group was also higher (P < 0.01) than that in the control group. The epigenetic control of genes related to important metabolic processes during the periconceptional period by nutritional conditions in utero and/or in vitro may have possible implication for the developmental programming during this period that may impact the welfare and production traits of farm animals.

关键词： B vitamin blastocyst epigenetics programming txnip

来源：评论

学校读者我要写书评

暂无评论

Ras Suppresses txnip Expression by Restricting Ribosome Translocation

引用

MOLECULAR AND CELLULAR BIOLOGY 2018年第20期38卷 e00178-18-e00178-18页

作者： Ye, Zhizhou Ayer, Donald E. Univ Utah Huntsman Canc Inst Dept Oncol Sci Salt Lake City UT 84112 USA

Oncogenic Ras upregulates aerobic glycolysis to meet the bioenergetic and biosynthetic demands of rapidly growing cells. In contrast, thioredoxin-interacting protein (txnip) is a potent inhibitor of glucose uptake and is frequently downregulated in human cancers. Our laboratory previously discovered that Ras activation suppresses txnip transcription and translation. In this study, we developed a system to study how Ras affects txnip translation in the absence of transcriptional effects. We show that whereas Ras drives a global increase in protein translation, it suppresses txnip protein synthesis by reducing the rate at which ribosomes transit the coding region of txnip mRNA. To investigate the underlying mechanism(s), we randomized or optimized the codons in the txnip message without altering the txnip primary amino acid sequence. Translation from these mRNA variants was still repressed by Ras, implying that mRNA secondary structure, microRNAs (miRNAs), RNA binding proteins, or codon usage does not contribute to the blockade of txnip synthesis. Rather, we show that the N terminus of the growing txnip polypeptide is the target for Ras-dependent translational repression. Our work demonstrates how Ras suppresses txnip translation elongation in the face of a global upregulation of protein synthesis and provides new insight into Ras-dependent metabolic reprogramming.

关键词： oncogenic Ras txnip translation elongation protein synthesis metabolic reprogramming Warburg effect glucose MondoA metabolic regulation translational control

来源：评论

学校读者我要写书评

暂无评论

Extracellular Matrix Remodeling Regulates Glucose Metabolism through txnip Destabilization

引用

CELL 2018年第1期175卷 117-+页

作者： Sullivan, William J. Mullen, Peter J. Schmid, Ernst W. Flores, Aimee Momcilovic, Milica Sharpley, Mark S. Jelinek, David Whiteley, Andrew E. Maxwell, Matthew B. Wilde, Blake R. Banerjee, Utpal Coller, Hilary A. Shackelford, David B. Braas, Daniel Ayer, Donald E. Vallim, Thomas Q. de Aguiar Lowry, William E. Christofk, Heather R. Univ Calif Los Angeles David Geffen Sch Med Dept Biol Chem Los Angeles CA 90095 USA Univ Calif Los Angeles David Geffen Sch Med Dept Mol & Med Pharmacol Los Angeles CA 90095 USA Univ Calif Los Angeles Dept Mol Cell & Dev Biol Los Angeles CA 90095 USA Univ Calif Los Angeles Mol Biol Inst Los Angeles CA 90095 USA Univ Calif Los Angeles David Geffen Sch Med Dept Pulm & Crit Care Med Los Angeles CA 90095 USA Univ Utah Huntsman Canc Inst Dept Oncol Sci Salt Lake City UT 84112 USA Univ Calif Los Angeles Eli & Edythe Broad Ctr Regenerat Med & Stem Cell Los Angeles CA 90095 USA Univ Calif Los Angeles Metabol Ctr Los Angeles CA 90095 USA Univ Calif Los Angeles David Geffen Sch Med Dept Med Los Angeles CA 90095 USA Univ Calif Los Angeles Jonsson Comprehens Canc Ctr Los Angeles CA 90095 USA

The metabolic state of a cell is influenced by cellextrinsic factors, including nutrient availability and growth factor signaling. Here, we present extracellular matrix (ECM) remodeling as another fundamental node of cell-extrinsic metabolic regulation. Unbiased analysis of glycolytic drivers identified the hyaluronan-mediated motility receptor as being among the most highly correlated with glycolysis in cancer. Confirming a mechanistic link between the ECM component hyaluronan and metabolism, treatment of cells and xenografts with hyaluronidase triggers a robust increase in glycolysis. This is largely achieved through rapid receptor tyrosine kinasemediated induction of the mRNA decay factor ZFP36, which targets txnip transcripts for degradation. Because txnip promotes internalization of the glucose transporter GLUT1, its acute decline enriches GLUT1 at the plasmamembrane. Functionally, induction of glycolysis by hyaluronidase is required for concomitant acceleration of cell migration. This interconnection between ECM remodeling and metabolism is exhibited in dynamic tissue states, including tumorigenesis and embryogenesis.

关键词： extracellular matrix glucose metabolism hyaluronidase receptor tyrosine kinase signaling ZFP36 mRNA degradation txnip GLUT1 trafficking cell migration cell biology

来源：评论

学校读者我要写书评

暂无评论

TLR4/NF-κB axis induces fludarabine resistance by suppressing txnip expression in acute myeloid leukemia cells

引用

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2018年第1期506卷 33-40页

作者： Huy, Hangsak Kim, Tae-Don Kim, Won Sam Kim, Dong Oh Byun, Jae-Eun Kim, Mi Jeong Park, Young-Jun Yoon, Suk Ran Noh, Ji-Yoon Lee, Jungwoon Lee, Kyoo-Hyung Choi, Inpyo Jung, Haiyoung KRIBB Immunotherapy Convergence Res Ctr Daejeon 34141 South Korea Univ Sci & Technol Dept Funct Genom Daejeon 34113 South Korea Chungbuk Natl Univ Sch Life Sci Dept Biochem Cheongju 28644 South Korea Univ Ulsan Coll Med Asan Med Ctr Dept Internal MedHematol Sect Seoul 05505 South Korea Univ Ulsan Coll Med Asan Med Ctr Dept Internal MedOncol Sect Seoul 05505 South Korea

Overcoming drug resistance is one of key issues in treating refractory acute myeloid leukemia (AML). The Toll-like receptor 4 (TLR4) signaling pathway is involved in many aspects of biological functions of AML cells, including the regulation of pro-inflammatory cytokine products, myeloid differentiation, and survival of AML cells. Thus, targeting TLR4 of AML patients for therapeutic purposes should be carefully addressed. In this regard, we investigated the possible role of TLR4 as a regulatory factor against fludarabine (FA) cytotoxicity activity. Here, we identified the differential expression of TLR4 and CD14 receptors in AML cell lines and examined their relationship to FA sensitivity. We found that the stimulation of TLR4 with lipopolysaccharide (LPS) in a TLR4-expressing cell line, THP-1, increased cell viability under FA treatment condition and showed that TLR4 stimulation overcame FA sensitivity through the activation of NF-kappa B, which subsequently upregulated several anti-apoptotic genes. The inhibition of TLR4/NF-kappa B signaling could partially or completely reverse LPS-induced cell survival under FA treatment conditions. Interestingly, we found that the expression of thioredoxin-interacting protein (txnip), a well-known tumor suppressor, was induced by FA treatment;however, it was suppressed by LPS treatment. Furthermore, the expression level of txnip was critical for FA-induced cytotoxicity or LPS-induced FA resistance of THP-1 cells. Our data suggest that txnip plays an important role in FA-induced cytotoxicity and TLR4/NF-kappa B-mediated FA resistance of AML cells. Therefore, txnip may be a potential therapeutic target for AML treatment. (C) 2018 Elsevier Inc. All rights reserved.

关键词： Fludarabine TLR4 NF-kappa B txnip AML

来源：评论

学校读者我要写书评

暂无评论

mROS-txnip axis activates NLRP3 inflammasome to mediate renal injury during ischemic AKI

引用

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 2018年 98卷 43-53页

作者： Wen, Yi Liu, Yi-Ran Tang, Tao-Tao Pan, Ming-Ming Xu, Sheng-Chun Ma, Kun-Ling Lv, Lin-Li Liu, Hong Liu, Bi-Cheng Southeast Univ Zhongda Hosp Inst Nephrol Sch Med Nanjing Jiangsu Peoples R China

Ischemia/reperfusion (I/R) is a critical risk factor for acute kidney injury (AKI). Recent studies provided evidence that tubular epithelial cells (TEC)-associated inflammation aggravates kidney injury and impairs tissue repair after I/R injury. Here we demonstrated that the Nod-like receptor protein 3 (NLRP3) inflammasome is activated by mitochondrial reactive oxygen species (mROS) during I/R injury via direct interactions between the inflammasome and thioredoxin-interacting protein (txnip). Firstly, we found that NLRP3 inflammasome activation was induced by I/R injury, peaking at day 3 after reperfusion. Consistent with this observation, NLRP3 deletion significantly attenuated I/R-induced kidney damage and markers of inflammasome activation. Then, we observed mitochondrial dysfunction, characterized by ultrastructural changes and cytochrome C (Cyt c) redistribution. Mitochondria-targeted antioxidant MitoTEMPO prevented mROS overproduction and the decline in mitochondrial membrane potential (MMP) in vitro. MitoTEMPO treatment also inhibited NLRP3 inflammasome activation and co-localization of NLRP3 and txnip after simulated ischemia/reperfusion (SI/R) injury. Finally, we transfected HK-2 cells with txnip siRNA to explore the role of txnip in mROS-induced NLRP3 inflammasome activation. We found that txnip siRNA significantly inhibited NLRP3 inflammasome activation. These results demonstrate that NLRP3 inflammasome is activated through the mROS-txnip-NLRP3 pathway and provide a potential therapeutic target in ischemic AKI.

关键词： Ischemic AKI NLRP3 inflammasome Mitochondrial dysfunction txnip

来源：评论

学校读者我要写书评

暂无评论

Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of txnip-NLRP3 inflammasome signal pathway

引用

FREE RADICAL BIOLOGY AND MEDICINE 2018年 120卷 368-379页

作者： Tang, Pan Gu, Jia-Ming Xie, Zi-Ang Gu, Yu Jie, Zhi-Wei Huang, Kang-Mao Wang, Ji-Ying Fan, Shun-Wu Jiang, Xue-Sheng Hu, Zhi-Jun Zhejiang Univ Sch Med Sir Run Run Shaw Hosp Dept Orthopaed 3 East Qingchun Rd Hangzhou 310016 Zhejiang Peoples R China Key Lab Biotherapy Zhejiang Prov 3 East Qingchun Rd Hangzhou 310016 Zhejiang Peoples R China Zhejiang Univ Huzhou Hosp Dept Orthopaed 198 Hongqi Rd Huzhou 313003 Peoples R China

Intervertebral disc degeneration (IVDD) is a multifactorial disease and responsible for many spine related disorders, causes disability in the workforce and heavy social costs all over the world. Honokiol, a low molecular weight natural product, could penetrate into and distribute in IVDs to achieve therapeutic effect in a rat tail model. Therefore, the present study was undertaken to examine the antiinflammatory, antioxidation and IVD-protective effect of honokiol using nucleus pulposus cells and investigate its mechanisms to provide a new basis for future clinical treatment of IVDD. In the current study, we demonstrated that honokiol inhibits the H2O2-induced apoptosis (caspase-9, caspase-3, and bax), levels of oxidative stress mediators (ROS, MDA), expression of inflammatory mediators (Interleukin-6, COX-2, and iNOS), major matrix degrading proteases (MMP-3, MMP-13, ADAMTS5, and ADAMTS4) associated with nucleus pulposus degradation. Furthermore, we found nucleus pulposus protective ability of honokiol by up-regulating extra cellular matrix anabolic factors like type II collagen (Col II) and SOX9 in nucleus pulposus. We also found that honokiol suppressed the phosphorylation of NFkB and JNK, and activation of txnip-NLRP3 inflammasome in H2O2-stimulated nucleus pulposus cells, thereby inhibiting the activation of downstream inflammatory mediators such as Interleukin-1 beta. Furthermore, honokiol showed a cartilage protective effect in the progression of IVDD in a rat model induced by puncture. Thus, our results demonstrate that honokiol inhibited the H2O2 induced apoptosis, oxidative stress, and inflammatory responses through the depression of txnip/NLRP3/caspase-1/ Interleukin - 1 beta signaling axis and the activation of NF-kB and JNK. Honokiol possess nucleus pulposus protective properties and may be of value in suppressing the pathogenesis of IVDD.

关键词： Intervertebral disc degeneration Honokiol txnip NLRP3 ROS

来源：评论

学校读者我要写书评

暂无评论

c-Myc-driven glycolysis via txnip suppression is dependent on glutaminase-MondoA axis in prostate cancer

引用

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2018年第2期504卷 415-421页

作者： Qu, Xuan Sun, Jing Zhang, Yami Li, Jun Hu, Junbi Li, Kai Gao, Lei Shen, Liangliang Shaanxi Univ Chinese Med Xianyang 712046 Peoples R China Fourth Mil Med Univ Dept Biochem & Mol Biol State Key Lab Canc Biol Xian 710032 Shaanxi Peoples R China Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Gastroenterol Xian 710061 Shaanxi Peoples R China Gen Hosp Xinjiang Mil Command Dept Clin Lab Xinjiang 830000 Peoples R China Wuhan Gen Hosp Guangzhou Mil Reg Dept Urol Wuhan 430070 Hubei Peoples R China

Oncogenic c-Myc-induced metabolic reprogramming triggers cellular dependency on exogenous glucose and glutamine. Understanding how nutrients are used may provide new target for therapeutic intervention. We previously provided an alternate route to c-Myc-driven glucose metabolism via the repression of thioredoxin-interacting protein (txnip), which is a potent negative regulator of glucose uptake. Herein, we demonstrate that c-Myc suppression of txnip is predominantly through the activation of glutaminolysis via glutaminase (GLS1) in prostate cancer cells. Glutamine depletion blocked c-Myc-dependent reductions of txnip and its principal regulator MondoA transcriptional activity. Further, GLS1 inhibition by either siRNA or CB-839 resumed txnip expression that was repressed by c-Myc. The txnip promoter with mutant E-Box region, which was recognized by MondoA, failed to respond to c-Myc or GLS1, indicating c-Myc repression of txnip by GLS1 is predominantly through the blockage of MondoA activity. Especially, ectopic txnip expression decreased c-Myc-induce glucose uptake and lead to a broad range of glycolytic target gene suppressions. Thus txnip is a key adaptor for c-Myc-driven aerobic glycolysis. Supporting the biological significance of c-Myc and txnip, their reciprocal relationship are correlates with patient outcome and contributes to the aggressive phenotype in PCAs. (C) 2018 Elsevier Inc. All rights reserved.

关键词： c-Myc txnip MondoA Glutaminolysis Glutaminase Prostate cancer

来源：评论

学校读者我要写书评

暂无评论

Mapping txnip: Key connexions in progression of diabetic nephropathy

引用

PHARMACOLOGICAL REPORTS 2018年第3期70卷 614-622页

作者： Kumar, Anil Mittal, Ruchika Panjab Univ UGC Ctr Adv Study Univ Inst Pharmaceut Sci Neuropharmacol Div Chandigarh India

Studies demonstrates the major involvement of inflammatory and apoptotic pathway in the pathophysiology of diabetic nephropathy. The cross talk between inflammatory and apoptotic pathway suggests txnip as a molecular connexion in progression of disease state. txnip modulates inflammatory pathway (via ROS production and NLRP3 inflammasome activity) and apoptotic pathway (via mTOR pathway). The key contribution of txnip in both the pathways, reflects, its crucial role in diabetic nephropathy. In the present review, we have first provided an overview of diabetic nephropathy and txnip system, followed by the mechanistic insight of txnip in the progression of diabetic nephropathy. This new mechanistic approach suggests to explore txnip modulators as a promising therapeutic drug target in diabetic nephropathy. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.

关键词： Diabetic nephropathy txnip Inflammation mTOR pathway

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：