检索结果-内蒙古大学图书馆

microRNA-135a-5p regulates NOD-like receptor family pyrin domain containing 3 inflammasome-mediated hypertensive cardiac inflammation and fibrosis via thioredoxin-interacting protein

引用

BIOENGINEERED 2022年第3期13卷 4658-4673页

作者： Chen, Hao Qiao, Huilian Zhao, Qiang Wei, Fuling Gen Hosp PLA Dept Cardiovasc Ctr Med Ctr 8 17 Heishan Hu Rd Beijing 100193 Peoples R China Air Force Med Ctr PLA Dept Pathol Beijing Peoples R China

Hypertension is a severe public health problem that induces cardiac injury with alterations of gene expressions. The current study sought to evaluate the mechanism of microRNA(miR)-135a-5p in NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediation of cardiac inflammation and hypertensive cardiac fibrosis. Firstly, hypertensive mouse models were established using angiotensin II (Ang II), followed by miR-135a-5p agomir treatment. Subsequently, mouse blood pressure and basic cardiac function indexes, histopathological changes, and cardiac fibrosis were all determined, in addition to detection of factors related to inflammation and fibrosis. Additionally, mice cardiac fibroblasts (CFs) were isolated and treated with Ang II. The binding relationship of miR-135a-5p and thioredoxin-interacting protein (txnip) was predicted and testified, while the interaction of txnip and NLRP3 was detected by means of a co-immunoprecipitation assay. It was found that miR-135a-5p was poorly-expressed in Ang II-treated mice and further exerted cardioprotective effects against hypertensive heart diseases. Moreover, over-expression of miR-135a-5p resulted in inhibition of inflammatory infiltration and almost eliminated cardiac fibrosis, as evidenced by decreased Collagen (COL)-I, COL-III, a-smooth muscle actin, NLRP3, tumor necrosis factor-alpha, and interleukin-6. Mechanically, miR-135a-5p inhibited txnip expression to block the binding of txnip and NLRP3. On the other hand, txnip up-regulation reversed the protective role of miR-135a-5p over-expression in CFs. Collectively, our findings indicated that miR-135a-5p over-expression inhibited txnip expression to block the binding of txnip and NLRP3, thereby alleviating hypertensive cardiac inflammation and fibrosis.

关键词： Hypertension cardiac fibrosis miR-135a-5p txnip NLRP3 cardiac inflammation proinflammatory factor protein-protein interaction

来源：评论

学校读者我要写书评

暂无评论

CORM-2 inhibits txnip/NLRP3 inflammasome pathway in LPS-induced acute lung injury

引用

INFLAMMATION RESEARCH 2016年第11期65卷 905-915页

作者： Jiang, Lei Fei, Dongsheng Gong, Rui Yang, Wei Yu, Wei Pan, Shangha Zhao, Mingran Zhao, Mingyan Harbin Med Univ Affiliated Hosp 1 Dept ICU Harbin Heilongjiang Pr Peoples R China Harbin Med Univ Affiliated Hosp 1 Dept Gen Surg Key Hepatosplen Surg Lab Harbin Heilongjiang Pr Peoples R China Childrens Hosp Harbin City Dept Pediat Harbin Peoples R China

Accumulated studies suggest that exogenously administered carbon monoxide is beneficial for the resolution of acute lung inflammation. The present study aimed to examine the effects and the underlying mechanisms of CORM-2 on thioredoxin-interacting protein (txnip)/NLRP3 inflammasome pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was intratracheally induced by LPS in C57BL6 mice. CORM-2 or iCORM-2 (30mg/kg i.p.) was administered immediately before LPS instillation. 6 h later, lung bronchoalveolar lavage (BAL) fluids were acquired for IL-18, IL-1 beta, and cell measurement, and lung issues were collected for histologic examination, wet/dry weight ratio, and determination of txnip/NLRP3 inflammasome expression, NLRP3 inflammasome and NF-IeB activity, and reactive oxygen species (ROS) production. LPS triggered significant lung edema, lung injury, and leukocyte infiltration, and elevated the levels of IL-1 beta and IL-18 in lung BAL fluids. CORM-2 pretreatment resulted in a marked amelioration of lung injury and reduced IL-1 beta and IL-18 secretion in BAL fluids. In lung tissues;CORM-2 down-regulated mRNA and protein level of txnip, NLRP3, ASC, and caspase-1. Furthermore, CORM-2 reduced ROS production, inhibited NLRP3 inflammasome and NF-kappa B activity, and interaction of txnip-NLRP3. However, no significant differences were detected between the LPS and iCORM-2 (an inactive variant of CORM-2) group. CORM-2 suppresses txnip/NLRP3 inflammasome pathway and protects against LPS-induced lung injury.

关键词： Carbon monoxide Acute lung injury NLRP3 inflammasome txnip

来源：评论

学校读者我要写书评

暂无评论

Thioredoxin interacting protein drives astrocytic glucose hypometabolism in corticosterone-induced depressive state

引用

JOURNAL OF NEUROCHEMISTRY 2022年第1期161卷 84-100页

作者： Pan, Shu-Man Pan, Ying Tang, Ya-Li Zuo, Na Zhang, Yan-Xiu Jia, Ke-Ke Kong, Ling-Dong Nanjing Univ Sch Life Sci State Key Lab Pharmaceut Biotechnol Nanjing 210023 Jiangsu Peoples R China

Brain energetics disturbance is a hypothesized cause of depression. Glucose is the predominant fuel of brain energy metabolism;however, the cell-specific change of glucose metabolism and underlying molecular mechanism in depression remains unclear. In this study, we firstly applied F-18-FDG PET and observed brain glucose hypometabolism in the prefrontal cortex (PFC) of corticosterone-induced depression of rats. Next, astrocytic glucose hypometabolism was identified in PFC slices in both corticosterone-induced depression of rats and cultured primary astrocytes from newborn rat PFC after stress-level corticosterone (100 nM) stimulation. Furthermore, we found the blockage of glucose uptake and the decrease of plasma membrane (PM) translocation of glucose transporter 1 (GLUT1) in astrocytic glucose hypometabolism under depressive condition. Interestingly, thioredoxin interacting protein (txnip), a glucose metabolism sensor and controller, was found to be over-expressed in corticosterone-stimulated astrocytes in vivo and in vitro. High txnip level could restrict GLUT1-mediated glucose uptake in primary astrocytes in vitro. Adeno-associated virus vector-mediated astrocytic txnip over-expression in rat medial PFC suppressed GLUT1 PM translocation, consequently developed depressive-like behavior. Conversely, txnip siRNA facilitated GLUT1 PM translocation to recover glucose hypometabolism in corticosterone-exposed cultured astrocytes. Notably, astrocyte-specific knockdown of txnip in medial PFC of rats facilitated astrocytic GLUT1 PM translocation, showing obvious antidepressant activity. These findings provide a new astrocytic energetic perspective in the pathogenesis of depression and, more importantly, provide txnip as a promising molecular target for novel depression therapy.

关键词： astrocytic glucose hypometabolism Depression GLUT1 translocation txnip

来源：评论

学校读者我要写书评

暂无评论

The anti-inflammatory feature of glucagon-like peptide-1 and its based diabetes drugs-Therapeutic potential exploration in lung injury

引用

Acta Pharmaceutica Sinica B 2022年第11期12卷 4040-4055页

作者： Juan Pang Jia Nuo Feng Wenhua Ling Tianru Jin Department of Nutrition School of Public HealthSun Yat-sen UniversitynstituteGuangzhou 510080China Division of Advanced Diagnostics Toronto General Hospital Research IUniversity Health NetworkToronto M5G 1L7Canada Department of Physiology Faculty of MedicineUniversity of TorontoToronto M5S 1AICanada Banting and Best Diabetes Centre Faculty of MedicineUniversity of ToromtoToronto M5G 2C4Canada

Since 2005,GLP-1 receptor(GLP-IR)agonists(GLP-IRAs)have been developed as therapeutic agents for type 2 diabetes(T2D).GLP-IR is not only expressed in pancreatic islets but also other organs,especially the ***,controversy on extra pancreatic GLP-IR expression still needs to be further resolved,utilizing different tools including the use of more reliable GLP-IR antibodies in immune-staining and ***-pancreatic expression of GLP-IR has triggered extensive investigations on extra-pancreatic functions of GLP-1RAs,aiming to repurpose them into therapeutic agents for other *** studies have demonstrated promising anti-infammatory features of *** those features are directly mediated by GLP-IR expressed in immune cells also remains *** a brief review on GLP-1 as an incretin hormone and the development of GLP-IRAs as therapeutic agents for T2D,we have summarized our current understanding of the antiinflammatory features of GLP-IRAS and commented on the controversy on extra-pancreatic GLP-IR *** main part of this review is a literature discussion on GLP-IRA utilization in animal models with chronic airway diseases and acute lung injuries,including studies on the combined use of mesenchymal stem cell(MSC)based *** is followed by a brief summary.

关键词： Anti inflammation Exenatide GLP-1R GLP-1RAs Liraglutide Lung injury MSC-based therapy txnip

来源：评论

学校读者我要写书评

暂无评论

Regulation of influenza A virus infection by Lnc-PINK1-2:5

引用

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 2022年第8期26卷 2285-2298页

作者： Pushparaj, Samuel Zhu, Zhengyu Huang, Chaoqun More, Sunil Liang, Yurong Lin, Kong Vaddadi, Kishore Liu, Lin Oklahoma State Univ Oklahoma Ctr Resp & Infect Dis Stillwater OK 74078 USA Oklahoma State Univ Dept Physiol Sci Lundberg Kienlen Lung Biol & Toxicol Lab Stillwater OK 74078 USA

Influenza virus causes approximately 291,000 to 646,000 human deaths worldwide annually. It is also a disease of zoonotic importance, affecting animals such as pigs, horses, and birds. Even though vaccination is being used to prevent influenza virus infection, there are limited options available to treat the disease. Long noncoding RNAs (lncRNAs) are RNA molecules with more than 200 nucleotides that do not translate into proteins. They play important roles in the physiological and pathological processes. In this study, we identified a novel transcript, Lnc-PINK1-2:5 that was upregulated by influenza virus. This lncRNA was predominantly located in the nucleus and was not affected by type I interferons. Overexpression of Lnc-PINK1-2:5 reduced the influenza viral mRNA and protein levels in cells as well as titres in culture media. Knockdown of Lnc-PINK1-2:5 using CRISPR interference enhanced the virus replication. Antiviral activity of Lnc-PINK1-2:5 was independent of influenza virus strains. RNA sequencing analysis revealed that Lnc-PINK1-2:5 upregulated thioredoxin interacting protein (txnip) during influenza virus infection. Overexpression of txnip reduced influenza virus infection, suggesting that txnip is an antiviral gene. Knockdown of txnip abolished the Lnc-PINK1-2:5-mediated increase in influenza virus infection. In conclusion, the newly identified Lnc-PINK1-2:5 isoform is an anti-influenza lncRNA acting through the upregulation of txnip gene expression.

关键词： antiviral host factors influenza virus Lnc-PINK1-2 long non-coding RNAs txnip

来源：评论

学校读者我要写书评

暂无评论

ADAMTS10 inhibits aggressiveness via JAK/STAT/c-MYC pathway and reprograms macrophage to create an anti-malignant microenvironment in gastric cancer

引用

GASTRIC CANCER 2022年第6期25卷 1002-1016页

作者： Zhou, Junyi Li, Tuoyang Chen, Hao Jiang, Yingming Zhao, Yandong Huang, Jintuan Chen, Zijian Tang, Xiaocheng Huang, Zhenze Yang, Zuli Sun Yat Sen Univ Affiliated Hosp 6 Dept Gastrointestinal Surg Sect 2 Guangzhou 510655 Peoples R China Sun Yat Sen Univ Affiliated Hosp 6 Guangdong Prov Key Lab Colorectal & Pelv Floor Di Guangzhou 510655 Peoples R China Sun Yat Sen Univ Affiliated Hosp 6 Dept Pathol Guangzhou 510655 Peoples R China

Background A disintegrin and metalloproteinase with thrombospondin motifs 10 (ADAMTS10) plays a role in extracellular matrix and correlates with Weill-Marchesani syndrome. However, its role in gastric cancer remains unknown. Thus, we started this research to unveil the role of ADAMTS10 in gastric cancer (GC). Methods The expression of ADAMTS10 in GC was analyzed by immunohistochemical staining and quantitative RT-PCR (qRT-PCR). The effects of ADAMTS10 inhibiting GC cell progression were conducted by functional experiments in vitro and in vivo. Flow cytometry was used to discover changing of cell cycle, apoptosis and ROS by ADAMTS10 in GC cell. Western blot was applied to identify targets of ADAMTS10. Western blot, qRT-PCR and flow cytometry were applied to discover the effect of ADAMT10 on THP1. Results ADAMTS10 expression was downregulated in GC tissue and patients with low ADAMTS10 levels had poorer overall survival. ADAMTS10 overexpression altered cell cycle, promoted apoptosis, and inhibited proliferation, migration, and invasion in vitro and in vivo. ADAMTS10 regulated txnip and ROS through the JAK/STAT/c-MYC pathway. Decreasing txnip and ROS reversed the inhibitory effect of ADAMTS10 on cell migration and invasion in vitro. ADAMTS10 secreted by GC cells was absorbed by THP1 and regulated txnip and ROS in THP1. ADAMTS10 secreted by GC cells inhibited macrophage M2 polarization. Conclusions These results suggest that ADAMTS10 targets txnip and ROS via the JAK/STAT/c-MYC pathway and that may play important roles in GC progression and macrophage polarization which indicates that ADAMTS10 can be a potential survival marker for gastric cancer.

关键词： ADAMTS10 Gastric cancer txnip JAK STAT c-MYC Macrophage

来源：评论

学校读者我要写书评

暂无评论

Thioredoxin-interacting protein regulates keratinocyte differentiation: Implication of its role in psoriasis

引用

FASEB JOURNAL 2022年第5期36卷 e22313-e22313页

作者： Hsiao, Pa-Fan Huang, Yi-Ting Lu, Po-Hsuan Chiu, Ling-Ya Weng, Tzu-Han Hung, Chi-Feng Wu, Nan-Lin MacKay Mem Hosp Dept Dermatol 92Sec 2Zhongshan N Rd Taipei 10449 Taiwan MacKay Med Coll Dept Med New Taipei Taiwan MacKay Jr Coll Med Nursing & Management Taipei Taiwan MacKay Mem Hosp Dept Med Res Taipei Taiwan Natl Taiwan Univ Coll Med Dept Pharmacol Taipei Taiwan MacKay Mem Hosp Dept Med Educ Taipei Taiwan Fu Jen Catholic Univ Sch Med New Taipei Taiwan Fu Jen Catholic Univ Grad Inst Biomed & Pharmaceut Sci New Taipei Taiwan MacKay Med Coll Inst Biomed Sci New Taipei Taiwan

Thioredoxin-interacting protein (txnip), also known as Vitamin-D upregulated protein-1 (VDUP-1), interacts with thioredoxin to regulate redox responses and participates in diverse disorders including metabolic, cardiovascular, inflammatory and malignant diseases. Psoriasis is characterized by chronic skin inflammation and an aberrant pattern of keratinocyte differentiation. Clinically, psoriasis is associated with various cardiometabolic comorbidities but studies on txnip's biological role in skin disorders are limited. In this study, we investigated txnip expression in psoriasis and its regulation in normal human epidermal keratinocytes (NHEKs), and then explored how txnip regulated skin keratinocyte differentiation to determine its role in psoriasis pathogenesis. Our immunohistochemical study demonstrated extensive txnip expression in the upper and lower epidermis of psoriasis compared to predominant txnip expression in the basal layer of normal skin. 1, 25-dihydroxyvitamin D-3 suppressed but TGF-alpha and EGF enhanced txnip expression in NHEKs. An inducer of keratinocyte differentiation, phorbol 12-myristate 13-acetate (PMA), also diminished txnip expression, which was reversed by PKC-delta knockdown. txnip knockdown reduced PMA-induced involucrin and transglutaminse-1 expression, and increased p63 expression in NHEKs but did not significantly affect cell proliferation. H2O2-induced ROS production and EGFR phosphorylation decreased in NHEKs with txnip knockdown. Furthermore, PMA-induced PKC-delta phosphorylation, TGF-alpha, and EGF-triggered EGFR phosphorylation were attenuated by txnip knockdown. Our results unraveled the regulation and function of txnip expression in skin keratinocytes and the cross-regulation between txnip and EGFR signaling. These findings imply a role of txnip in psoriasis and provide insight into the possible impact of txnip regulators on the skin or psoriasis.

关键词： differentiation EGFR keratinocyte psoriasis txnip

来源：评论

学校读者我要写书评

暂无评论

A Novel Long-Noncoding RNA LncZFAS1 Prevents MPP⁺-Induced Neuroinflammation Through MIB1 Activation

引用

MOLECULAR NEUROBIOLOGY 2022年第2期59卷 778-799页

作者： Zhu, Ziman Huang, Peiling Sun, Ruifeng Li, Xiaoling Li, Wenshan Gong, Weijun Capital Med Univ Beijing Rehabil Med Acad Beijing 100144 Peoples R China Capital Med Univ Beijing Rehabil Hosp Dept Neurol Rehabil Beijing 100144 Peoples R China

Parkinson's disease remains one of the leading neurodegenerative diseases in developed countries. Despite well-defined symptomology and pathology, the complexity of Parkinson's disease prevents a full understanding of its etiological mechanism. Mechanistically, alpha-synuclein misfolding and aggregation appear to be central for disease progression, but mitochondrial dysfunction, dysfunctional protein clearance and ubiquitin/proteasome systems, and neuroinflammation have also been associated with Parkinson's disease. Particularly, neuroinflammation, which was initially thought to be a side effect of Parkinson's disease pathogenesis, has now been recognized as driver of Parkinson's disease exacerbation. Next-generation sequencing has been used to identify a plethora of long noncoding RNAs (lncRNA) with important transcriptional regulatory functions. Moreover, a myriad of lncRNAs are known to be regulators of inflammatory signaling and neurodegenerative diseases, including IL-1 beta secretion and Parkinson's disease. Here, LncZFAS1 was identified as a regulator of inflammasome activation, and pyroptosis in human neuroblast SH-SY5Y cells following MPP+ treatment, a common in vitro Parkinson's disease cell model. Mechanistically, txnip ubiquitination through MIB1 E3 ubiquitin ligase regulates NLRP3 inflammasome activation in neuroblasts. In contrast, MPP+ activates the NLPR3 inflammasome through miR590-3p upregulation and direct interference with MIB1-dependent txnip ubiquitination. LncZFAS overexpression inhibits this entire pathway through direct interference with miR590-3p, exposing a novel research idea regarding the mechanism of Parkinson's disease.

关键词： LncZFAS Parkinson's disease Pyroptosis MIB1 txnip NLRP3

来源：评论

学校读者我要写书评

暂无评论

txnip基因敲除抑制糖尿病诱导的小鼠睾丸生精细胞凋亡与氧化压力

Txnip基因敲除抑制糖尿病诱导的小鼠睾丸生精细胞凋亡与氧化压力

引用

作者：吴余重庆医科大学

学位级别：硕士

实验目的:硫氧还蛋白互作蛋白(thioredoxin-interacting protein,txnip)发现于1,25-二羟维生素D3处理的HL-60细胞,因此早前命名为维生素D3上调蛋白1(vitamin D3 upregulated protein 1,VDUP1)。txnip可以与硫氧还蛋白(thioredoxin,Trx)结合,从而抑制Trx的抗氧化功能,导致活性氧的累积与细胞压力。经葡萄糖处理后,txnip在人胰岛中表达高度上调,具有平衡代谢和调节细胞生长、分化的功能。但txnip在雄性睾丸中的表达定位与功能研究尚未见报道,是否在糖尿病导致的雄性生殖功能受损中扮演某种角色值得研究。基于此,本研究拟通过制备糖尿病小鼠模型,观察txnip基因敲除是否具有拮抗睾丸损伤的效应及其可能的机制,为临床上防治糖尿病生殖损伤提供实验依据。实验方法:1.免疫组化、免疫荧光、PCR和western blot方法检测txnip在小鼠睾丸中表达情况。2.繁殖txnip基因敲除小鼠(TALEN技术制备)与野生型小鼠,用于糖尿病模型制备。首次注射链脲佐菌素(streptozotocin,STZ)前禁食12 h,按55 mg/kg剂量腹腔内注射STZ,连续5d。实验分组:野生型小鼠组(WT)、txnip基因敲除组(KO)、WT+STZ组和KO+STZ组,每组6只小鼠。6 d后用血糖测定仪(ACCU CHEK,罗氏)检测血糖。野生型小鼠血糖大于16.7 mmol/L视为造模成功。常规饲养60 d后处死小鼠,取血液与睾丸标本,用于进一步实验。3.免疫组化、western blot检测txnip基因敲除对小鼠睾丸txnip表达的影响。睾丸标本制成石蜡切片,通过HE染色和TUNEL实验观察小鼠睾丸的形态学变化及检测精细胞的凋亡情况。并且测定小鼠睾丸组织中MDA含量与SOD活性。实验结果:1.免疫组化、免疫荧光、PCR及western blot实验结果显示txnip表达于小鼠睾丸组织中支持细胞、间质细胞及精细胞区域;体外实验显示txnip表达于睾丸TM4支持细胞及TM3间质细胞的胞质。2.免疫组化与western blot实验结果表明在txnip敲除小鼠睾丸中未检测到txnip表达。STZ诱导野生型小鼠血糖明显增加,txnip基因敲除明显抑制血糖的增加。3.睾丸组织学结果显示txnip基因敲除抑制睾丸形态学损伤与生精细胞凋亡,下调凋亡相关蛋白Bax/Bcl-2表达比值。此外,txnip敲除明显下调糖尿病小鼠模型睾丸MDA水平,上调SOD活性。实验结论:txnip表达在小鼠睾丸组织中支持细胞、间质细胞及精细胞区域,体外实验显示txnip表达于TM4支持细胞及TM3间质细胞的胞质。STZ可以诱导血糖上升,但敲除txnip明显抑制血糖的增加。通过分析睾丸形态学,发现txnip基因敲除抑制睾丸形态学损伤与生精细胞凋亡,下调凋亡相关蛋白Bax/Bcl-2表达比值。此外,txnip敲除明显下调糖尿病小鼠模型睾丸MDA水平,上调SOD活性。本研究揭示txnip基因敲除可以拮抗高血糖引起的睾丸生精细胞凋亡与氧化压力增加,从而有效发挥抗生殖损伤的作用。进一步研究其机理对防治糖尿病导致的雄性生殖功能异常具有重要意义。

关键词： txnip 生殖功能糖尿病凋亡氧化压力

来源：评论

学校读者我要写书评

暂无评论

txnip在衰老导致的胰岛β细胞功能障碍中的作用及其机制研究

TXNIP在衰老导致的胰岛β细胞功能障碍中的作用及其机制研究

引用

作者：李杨重庆医科大学

学位级别：硕士

第一部分高脂饲养促进衰老导致的胰岛功能障碍及txnip表达目的:探讨衰老在胰腺功能障碍中的作用及衰老与txnip表达的关系。方法:收集不同年龄段(青年、中年、老年)正常人体胰腺组织标本,用免疫组化方法检测txnip蛋白表达水平。48只4周龄... 详细信息

第一部分高脂饲养促进衰老导致的胰岛功能障碍及txnip表达目的:探讨衰老在胰腺功能障碍中的作用及衰老与txnip表达的关系。方法:收集不同年龄段(青年、中年、老年)正常人体胰腺组织标本,用免疫组化方法检测txnip蛋白表达水平。48只4周龄C57BL/6J小鼠随机均分为普食组和高脂组,两组再按照4个时间段(3个月、6个月、9个月、12个月)饲养至所需月龄。观察小鼠一般生长情况,检测各年龄段各组小鼠GTT、ITT及基础代谢指标,检测txnip、TRX及衰老相关蛋白p16的表达水平。结果:随着年龄的增长,正常人体胰岛中txnip表达水平增加(p<0.01)。随着年龄的增长,小鼠空腹血糖逐渐增高(p<0.05),小鼠胰岛素分泌水平逐渐下降(p<0.05),胰岛素抵抗逐渐增加(p<0.05);与同月龄普食组小鼠相比,6、9、12月龄高脂组小鼠空腹血糖较高(p<0.01);各月龄普食组小鼠胰岛素分泌功能均较好,胰岛素抵抗均较轻。随着年龄增加,高脂组小鼠血中TC、TG、LDL含量逐渐增加(p<0.01)。随着年龄增加,胰腺组织中txnip、P16蛋白表达逐渐增加,TRX蛋白表达逐渐降低(均p<0.05)。同年龄段小鼠胰腺组织,与普食组相比,9、12月龄高脂组的txnip表达水平明显升高(p<0.05);3、6、12月龄高脂组的p16表达水平明显升高(p<0.05),而TRX表达水平较低(p<0.05)。结论:高脂饲养促进衰老导致的小鼠胰岛素分泌功能降低和胰岛素抵抗增加,促进小鼠代谢紊乱,同时促进衰老导致的胰腺组织txnip表达增加。第二部分txnip促进衰老导致的胰岛功能障碍目的:探讨txnip在衰老导致的胰岛功能障碍中的作用和机制方法:24只4周龄C57BL/6J小鼠(WT)和txnip基因敲出鼠(txnip-/-),按照4个时间段(3个月、6个月、9个月、12个月)普食饲养至所需月龄。观察小鼠一般生长情况,检测各年龄段各组小鼠GTT、ITT及基础代谢指标,检测txnip、TRX及衰老相关蛋白p16的表达水平。结果:与同年龄段WT小鼠相比,txnip-/-组小鼠空腹血糖较低(p<0.05),小鼠胰岛素分泌功能较好(p<0.05),胰岛素抵抗较弱(p<0.05)。与同年龄段WT小鼠相比,各月龄txnip-/-组的体重均较低((p<0.05);6、9、12月龄txnip-/-组的TG较低(p<0.05);9、12月龄LDL较低(p<0.05)。同年龄段小鼠胰腺组织,与WT小鼠相比较,9、12月龄txnip-/-组的TRX表达水平明显较高(p<0.01);6、9、12月龄txnip-/-组的P16表达水平明显较低(p<0.05)。结论:txnip促进衰老导致的胰岛素分泌功能减弱和胰岛素抵抗,促进衰老导致的小鼠代谢紊乱和衰老相关蛋白p16的表达。第三部分txnip促进胰岛β细胞衰老的作用及相关机制目的:研究txnip和EZH2对MIN6细胞衰老的影响及其相关机制及其相互作用关系。方法:将处于对数生长期的MIN6细胞,进行EZH2、txnip过表达及txnip沉默慢病毒转染,用荧光显微镜和Westen-blot方法检测转染效能。将MIN6细胞分为空载组(LV-GFP)组、txnip过表达(LV-txnip)组和txnip沉默组(LV-txnipsi RNA)组。利用流式测定细胞周期;利用CCK-8评估细胞增值活力;采用Annexin V/PI双染色法检测细胞凋亡;用DHE法测定ROS表达;用Westen-blot法检测txnip、TRX、p16、活化的Caspase蛋白的表达水平及p38 MAPK通路激活水平。结果:感染慢病毒72小时后,病毒转染成功。与LV-GFP组相比较,LV-GFP-txnip组的增殖出现G1-S期阻滞,细胞生存率明显降低,而其凋亡率和ROS水平明显增加,p16、活化的Caspase3蛋白表达及p38 MAPK磷酸化水平明显增高(均P<0.01)。LV-GFP-txnipsi RNA组和LV-EZH2组的细胞生存率明显升高,而其凋亡率和ROS水平明显降低(均P<0.01),P16、活化的Caspase3蛋白表达及p38 MAPK磷酸化水平明显降低(均P<0.05)。LV-EZH2组的p16、txnip蛋白表达明显增高(均P<0.01),且TRX蛋白表达明显降低(P<0.01)。其次,p38MAPK特异性抑制剂作用后,LV-GFP-txnip组的p16及活化的Caspase3蛋白表达均显著减少(均P<0.01)。结论:txnip表达上调能够抑制MIN6细胞增殖,促进细胞的衰老和凋亡,且p38 MAPK信号通路可能参与其中,同时,过表达EZH2能增加细胞生存率,减少细胞的凋亡和过氧化物的产生,其可能机制为EZH2可通过抑制TXN

关键词：衰老胰岛功能障碍 txnip 衰老胰岛功能障碍 txnip 衰老胰岛β细胞 txnip EZH2

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：