scholarly journals The Critical Role of Thioredoxin-Interacting Protein in Shear-Related Inflammatory Response in Diabetes

2016 ◽  
Vol 25 ◽  
pp. S91
Author(s):  
J. Ciofani ◽  
J. Yuan ◽  
P. Simpson ◽  
E. King ◽  
L. Khoo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

scholarly journals Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Signaling Complex ◽  
Current Review ◽  
Wide Range ◽  
Range Of Functions ◽  
Species Production ◽  
And Oxidative Stress ◽  
Significant Attention

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

scholarly journals Endothelial pro-atherosclerotic response to extracellular diabetic-like environment: Possible role of thioredoxin-interacting protein

2010 ◽  
Vol 25 (7) ◽  
pp. 2141-2149 ◽  
Author(s):  
T. Zitman-Gal ◽  
J. Green ◽  
M. Pasmanik-Chor ◽  
V. Oron-Karni ◽  
J. Bernheim
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP

2019 ◽  
Author(s):  
Rui Ding ◽  
ZhengTao Gu ◽  
ChangSheng Yang ◽  
CaiQiang Huang ◽  
QingChu Li ◽  
...  
Keyword(s):  
Interacting Protein ◽  
Blood Samples ◽  
Rat Models ◽  
Thioredoxin Interacting Protein ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Rat Osteoblasts

Abstract BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.

scholarly journals A Critical Role of c-Cbl-Interacting Protein of 85 kDa in the Development and Progression of Head and Neck Squamous Cell Carcinomas through the Ras-ERK Pathway

Neoplasia ◽  
2010 ◽  
Vol 12 (10) ◽  
pp. 789-IN4 ◽  
Author(s):  
Takahiro Wakasaki ◽  
Muneyuki Masuda ◽  
Hiroaki Niiro ◽  
Siamak Jabbarzadeh-Tabrizi ◽  
Kumiko Noda ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Critical Role ◽  
Squamous Cell Carcinomas ◽  
Erk Pathway ◽  
Interacting Protein

scholarly journals Differential HspBP1 expression accounts for the greater vulnerability of neurons than astrocytes to misfolded proteins

2017 ◽  
Vol 114 (37) ◽  
pp. E7803-E7811 ◽  
Author(s):  
Ting Zhao ◽  
Yan Hong ◽  
Peng Yin ◽  
Shihua Li ◽  
Xiao-Jiang Li
Keyword(s):  
Neurodegenerative Diseases ◽  
Critical Role ◽  
Misfolded Proteins ◽  
Inhibitory Protein ◽  
Interacting Protein ◽  
C Terminus ◽  
Differential Vulnerability ◽  
Disease Protein ◽  
Knockin Mouse

Although it is well known that astrocytes are less vulnerable than neurons in neurodegenerative diseases, the mechanism behind this differential vulnerability is unclear. Here we report that neurons and astrocytes show markedly different activities in C terminus of Hsp70-interacting protein (CHIP), a cochaperone of Hsp70. In astrocytes, CHIP is more actively monoubiquitinated and binds to mutant huntingtin (mHtt), the Huntington’s disease protein, more avidly, facilitating its K48-linked polyubiquitination and degradation. Astrocytes also show the higher level and heat-shock induction of Hsp70 and faster CHIP-mediated degradation of various misfolded proteins than neurons. In contrast to astrocytes, neurons express abundant HspBP1, a CHIP inhibitory protein, resulting in the low activity of CHIP. Silencing HspBP1 expression via CRISPR-Cas9 in neurons ameliorated mHtt aggregation and neuropathology in HD knockin mouse brains. Our findings indicate a critical role of HspBP1 in differential CHIP/Hsp70 activities in neuronal and glial cells and the greater neuronal vulnerability to misfolded proteins in neurodegenerative diseases.

scholarly journals Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein

2009 ◽  
Vol 296 (5) ◽  
pp. E1133-E1139 ◽  
Author(s):  
Junqin Chen ◽  
Hyunjoo Cha-Molstad ◽  
Anna Szabo ◽  
Anath Shalev
Keyword(s):  
Calcium Channel ◽  
Diabetic Cardiomyopathy ◽  
Calcium Channel Blockers ◽  
Caspase 3 ◽  
Critical Role ◽  
Cardiomyocyte Apoptosis ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Cardiomyocyte apoptosis is a critical process in the pathogenesis of ischemic and diabetic cardiomyopathy, but the mechanisms are not fully understood. Thioredoxin-interacting protein (TXNIP) has recently been shown to have deleterious effects in the cardiovascular system and we therefore investigated whether it may also play a role in diabetes-associated cardiomyocyte apoptosis. In fact, TXNIP expression was increased in H9C2 cardiomyocytes incubated at high glucose, and cardiac expression of TXNIP and cleaved caspase-3 were also elevated in vivo in streptozotocin- and obesity-induced diabetic mice. Together, these findings not only suggest that TXNIP is involved in diabetic cardiomyopathy but also that it may represent a novel therapeutic target. Surprisingly, testing putative TXNIP modulators revealed that calcium channel blockers reduce cardiomyocyte TXNIP transcription and protein levels in a dose-dependent manner. Oral administration of verapamil for 3 wk also reduced cardiac TXNIP expression in mice even in the face of severe diabetes, and these reduced TXNIP levels were associated with decreased apoptosis. To determine whether lack of TXNIP can mimic the verapamil-induced decrease in apoptosis, we used TXNIP-deficient HcB-19 mice, harboring a natural nonsense mutation in the TXNIP gene. Interestingly, we found significantly reduced cleaved caspase-3 levels in HcB-19 hearts, suggesting that TXNIP plays a critical role in cardiac apoptosis and that the verapamil effects were mediated by TXNIP reduction. Thus our results suggest that TXNIP reduction is a powerful target to enhance cardiomyocyte survival and that agents such as calcium channel blockers may be useful in trying to achieve this goal and prevent diabetic cardiomyopathy.

scholarly journals Protective role of microRNA-9-5p in oxygen glucose deprivation/reperfusion-induced injury in liver sinusoidal endothelial cell

2020 ◽  
Author(s):  
Yi Duan ◽  
Zhifeng Gao ◽  
Xiaoyu Wang ◽  
Yuanyuan Meng ◽  
Huan Zhang
Keyword(s):  
Inflammatory Response ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Glucose Deprivation ◽  
Protective Role ◽  
Liver Sinusoidal Endothelial Cell ◽  
Liver Sinusoidal Endothelial Cells ◽  
Hepatic Ischemia

Abstract Background: Maintenance of the function and survival of liver sinusoidal endothelial cells (LSECs) play a crucial role in hepatic ischemia/reperfusion (I/R) injury, a major cause of liver impairment during surgical treatment. Emerging evidence indicate a critical role of microRNAs in I/R injury. This study aims to investigate whether miR-9-5p exert a protective effect on LSECs in vitro .Methods: We transfected LSECs with miR-9-5p mimic or mimic NC. LSECs were treated with oxygen and glucose deprivation (OGD, 5% CO2 and 95% N2), followed by glucose-free DMEM medium for 6 h, and high-glucose (HG, 30 mmol/L glucose) DMEM medium for 12 h. The biological role of miR-9-5p in I/R-induced LSEC injury was determined. Results: In the in vitro model of OGD/HG injury in LSECs, the expression levels of miR-9-5p were significantly downregulated and those of CXC chemokine receptor-4 (CXCR4) upregulated. LSEC I/R injury led to deteriorated cell death, enhanced oxidative stress and excessive inflammatory response. Mechanistically, we showed that miR-9-5p overexpression significantly upregulated both mRNA and protein levels of CXCR4, followed by rescue of LSECs, ameliorated inflammatory response, and deactivation of pro-apoptotic signaling pathways.Conclusion: miR-9-5p promotes LSEC survival and inhibits apoptosis and inflammatory response in LSECs following OGD/HG injury via downregulation of CXCR4.

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