scholarly journals The Chx10-Traf3 Knockout Mouse as a Viable Model to Study Neuronal Immune Regulation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2068
Author(s):  
Jami M. Gurley ◽  
Grzegorz B. Gmyrek ◽  
Elizabeth A. Hargis ◽  
Gail A. Bishop ◽  
Daniel J. J. Carr ◽  
...  
Keyword(s):  
Immune Regulation ◽  
Knockout Mouse ◽  
Immune Cell ◽  
Tumor Necrosis Factor Receptor ◽  
Therapeutic Interventions ◽  
Knockout Mouse Model ◽  
Retinal Structure ◽  
And Function ◽  
Viable Model ◽  
Necrosis Factor

Uncontrolled inflammation is associated with neurodegenerative conditions in central nervous system tissues, including the retina and brain. We previously found that the neural retina (NR) plays an important role in retinal immunity. Tumor necrosis factor Receptor-Associated Factor 3 (TRAF3) is a known immune regulator expressed in the retina; however, whether TRAF3 regulates retinal immunity is unknown. We have generated the first conditional NR-Traf3 knockout mouse model (Chx10-Cre/Traf3f/f) to enable studies of neuronal TRAF3 function. Here, we evaluated NR-Traf3 depletion effects on whole retinal TRAF3 protein expression, visual acuity, and retinal structure and function. Additionally, to determine if NR-Traf3 plays a role in retinal immune regulation, we used flow cytometry to assess immune cell infiltration following acute local lipopolysaccharide (LPS) administration. Our results show that TRAF3 protein is highly expressed in the NR and establish that NR-Traf3 depletion does not affect basal retinal structure or function. Importantly, NR-Traf3 promoted LPS-stimulated retinal immune infiltration. Thus, our findings propose NR-Traf3 as a positive regulator of retinal immunity. Further, the NR-Traf3 mouse provides a tool for investigations of neuronal TRAF3 as a novel potential target for therapeutic interventions aimed at suppressing retinal inflammatory disease and may also inform treatment approaches for inflammatory neurodegenerative brain conditions.

Ablation of adipose-HO-1 expression increases white fat over beige fat through inhibition of mitochondrial fusion and of PGC1α in female mice

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Shailendra P. Singh ◽  
Ilana Grant ◽  
Aliza Meissner ◽  
Attallah Kappas ◽  
Nader G. Abraham
Keyword(s):  
Adipose Tissue ◽  
Knockout Mouse ◽  
Potential Role ◽  
Mitochondrial Quality Control ◽  
Knockout Mouse Model ◽  
Genetic Ablation ◽  
Beige Fat ◽  
And Function ◽  
White Fat

AbstractBackgroundHmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction.MethodsWe investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1ResultsAdipo-HO-1ConclusionAblation of adipose tissue-HO-1 abridged PGC1 expression promoted mitochondrial dysfunction and contributed to an increase of pro-inflammatory visceral fat and abrogated beige-cell like phenotype.

scholarly journals Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers

2021 ◽  
Vol 27 ◽  
Author(s):  
Seong Won Moon ◽  
Hyun Ji Son ◽  
Eun Ji Choi ◽  
Nam Jin Yoo ◽  
Sug Hyung Lee
Keyword(s):  
Regional Difference ◽  
Tumor Necrosis Factor Receptor ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
Research Report ◽  
Colon Cells ◽  
Frameshift Mutations ◽  
Colon Cancers ◽  
And Function ◽  
Necrosis Factor

TRAF2 and TRAF3 genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of TRAF2 and TRAF3 in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed TRAF2 and TRAF3 frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68 microsatellite-stable (MSS) CCs). We identified TRAF2 and TRAF3 frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs, we analyzed the mutations in multi-regions for 39 CCs (16 MSI-H and 23 MSS CCs), and discovered that 12.5% (2/16) and 6.3% (1/16) of MSI-H CCs exhibited regional difference in TRAF2 and TRAF3 mutations, respectively. In the multi-region samples of 23 MSS CCs, neither TRAF2 nor TRAF3 frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that TRAF2 and TRAF3 frameshift mutations and their regional difference as well as altered expressions are present in MSI-H CCs, which could contribute to MSI-H cancer development.

scholarly journals Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions

2011 ◽  
Vol 244 (1) ◽  
pp. 55-74 ◽  
Author(s):  
Joanne M. Hildebrand ◽  
Zuoan Yi ◽  
Claire M. Buchta ◽  
Jayakumar Poovassery ◽  
Laura L. Stunz ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Immune Cell ◽  
Tumor Necrosis Factor Receptor ◽  
Associated Factor ◽  
Cell Functions ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor Receptor-Associated Protein 1 Protects against Mitochondrial Injury by Preventing High Glucose-Induced mPTP Opening in Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Lerong Liu ◽  
Lingxiao Zhang ◽  
Jiangpei Zhao ◽  
Xiangyu Guo ◽  
Yuanyuan Luo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
High Glucose ◽  
Tumor Necrosis ◽  
Mitochondrial Permeability Transition ◽  
Tumor Necrosis Factor Receptor ◽  
Mitochondrial Morphology ◽  
Receptor Associated Protein ◽  
Mptp Opening ◽  
And Function ◽  
Necrosis Factor

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Renal tubular epithelial cell apoptosis and tubular atrophy have been recognized as indicators of the severity and progression of DKD, while the mechanism remains elusive. Tumor necrosis factor receptor-associated protein 1 (TRAP1) plays critical roles in apoptosis. The aim of this study was to investigate the protective role TRAP1 plays in DKD and to study the potential underlying mechanisms. TRAP1 expression was decreased, and mitochondria were injured in NRK-52e cells under high-glucose (HG) conditions. The overexpression of TRAP1 ameliorated HG-induced apoptosis, increased cell viability, maintained mitochondrial morphology, adenosine triphosphate (ATP) levels, and mitochondrial membrane potential (MMP), and buffered oxidative stress, whereas TRAP1 knockdown aggravated these effects. The protective effects of TRAP1 may be exerted via the inhibition of mitochondrial permeability transition pore (mPTP) opening, and the damage caused by TRAP1 knockdown can be partially reversed by treatment with the mPTP opening inhibitor cyclosporin A (CsA). In vivo, TRAP1 expression upregulation by AAV2/9 injection prevented renal dysfunction, ameliorated histopathological changes, maintained mitochondrial morphology and function, and reduced apoptosis and reactive oxygen species (ROS) in STZ-treated DKD rats. Thus, our results suggest that TRAP1 ameliorates diabetes-induced renal injury by preventing abnormal mPTP opening and maintaining mitochondrial structure and function, which may be treated as a potential target for DKD treatment.

scholarly journals Epigenetic Dynamics of the Infant Immune System Reveals a Tumor Necrosis Factor Superfamily Signature in Early Human Life

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 12
Author(s):  
Maria J. Gutierrez ◽  
Gustavo Nino ◽  
Xiumei Hong ◽  
Xiaobin Wang
Keyword(s):  
Dna Methylation ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Immune Cell ◽  
Human Life ◽  
Tumor Necrosis Factor Receptor ◽  
Immune Genes ◽  
Cpg Sites ◽  
Necrosis Factor

DNA methylation (DNAm) is an essential mechanism governing normal development in humans. Although most DNAm patterns in blood cells are established in utero, the genes associated with immune function undergo postnatal DNAm modifications, and the characterization of this subset of genes is incomplete. Accordingly, we used available longitudinal DNAm datasets from a large birth cohort in the U.S. to further identify postnatal DNAm variation in peripheral leukocytes from 105 children (n = 105) between birth and the first two years of life, as determined by postnatal changes in β values (with the percentage of methylation ranging from 0 to 1.0 at individual CpG sites). Our study is an extension of a previous analysis performed by our group and identified that: (1) as previously described, DNAm patterns at most CpG sites were established before birth and only a small group of genes underwent DNAm modifications postnatally, (2) this subset includes multiple immune genes critical for lymphocyte development, and (3) several members of the tumor necrosis factor receptor and cytokine superfamilies with essential roles in immune cell activation, survival, and lymphoid tissue development were among those with a larger postnatal variation. This study describes the precise epigenetic DNA methylation marks in important immune genes that change postnatally and raises relevant questions about the role of DNAm during postnatal immune development in early childhood.

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