Kainic Acid-Activated Microglia Mediate Increased Excitability of Rat Hippocampal Neurons in vitro and in vivo: Crucial Role of Interleukin-1beta

2010 ◽  
Vol 17 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Honghua Zheng ◽  
Wei Zhu ◽  
Hu Zhao ◽  
Xiaojing Wang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Crucial Role ◽  
Hippocampal Neurons ◽  
Activated Microglia ◽  
Interleukin 1Beta

scholarly journals Crucial Role of Nucleic Acid Sensing via Endosomal Toll-Like Receptors for the Defense of Streptococcus pyogenes in vitro and in vivo

2019 ◽  
Vol 10 ◽  
Author(s):  
Anna Hafner ◽  
Ulrike Kolbe ◽  
Isabel Freund ◽  
Virginia Castiglia ◽  
Pavel Kovarik ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Streptococcus Pyogenes ◽  
Crucial Role ◽  
Toll Like Receptors

654 Crucial role of Dickkopf-3 in prostate morphogenesis in vitro and in vivo

2012 ◽  
Vol 11 (1) ◽  
pp. e654-e654a
Author(s):  
Y. Kawano ◽  
D. Romero ◽  
N. Bengoa ◽  
N. Maltry ◽  
M. Walker ◽  
...  
Keyword(s):  
Crucial Role ◽  
Morphogenesis In Vitro

Excitotoxicity of TNFα derived from KA activated microglia on hippocampal neurons in vitro and in vivo

2010 ◽  
Vol 114 (2) ◽  
pp. 386-396 ◽  
Author(s):  
Wei Zhu ◽  
Honghua Zheng ◽  
Xinli Shao ◽  
Wei Wang ◽  
Qing Yao ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Activated Microglia

A crucial role of β1 integrins for keratinocyte migration in vitro and during cutaneous wound repair

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2303-2315 ◽  
Author(s):  
Richard Grose ◽  
Caroline Hutter ◽  
Wilhelm Bloch ◽  
Irmgard Thorey ◽  
Fiona M. Watt ◽  
...  
Keyword(s):  
Crucial Role ◽  
Wound Repair ◽  
Proliferation Rate ◽  
Cutaneous Wound ◽  
Keratinocyte Migration ◽  
Β1 Integrins ◽  
Cell Matrix Interactions

Integrins are ubiquitous transmembrane receptors that play crucial roles in cell-cell and cell-matrix interactions. In this study, we have determined the effects of the loss of β1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured β1-deficient keratinocytes confirmed the absence of β1 integrins and showed downregulation of α6β4 but not of αv integrins. β1-null keratinocytes were characterised by poor adhesion to various substrates, by a reduced proliferation rate and by a strongly impaired migratory capacity. In vivo, the loss of β1 integrins in keratinocytes caused a severe defect in wound healing. β1-null keratinocytes showed impaired migration and were more densely packed in the hyperproliferative epithelium. Surprisingly, their proliferation rate was not reduced in early wounds and even increased in late wounds. The failure in re-epithelialisation resulted in a prolonged inflammatory response, leading to dramatic alterations in the expression of important wound-regulated genes. Ultimately, β1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of β1 integrins in keratinocyte migration and wound re-epithelialisation. Movies available on-line

scholarly journals LncRNA UCA1 alleviates aberrant hippocampal neurogenesis through regulating miR-375/SFRP1-mediated WNT/β-catenin pathway in kainic acid-induced epilepsy

2021 ◽  
Author(s):  
Limei Diao ◽  
Haichun Yu ◽  
Huaqiong Li ◽  
Yueqiang Hu ◽  
Mingfen Li ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Hippocampal Neurons ◽  
Pearson Correlation ◽  
Hippocampal Neurogenesis ◽  
Neural Progenitors ◽  
Luciferase Assay ◽  
Control Group ◽  
Non Coding Rna

Temporal lobe epilepsy (TLE) is a chronic disease of the nervous system, associated with increased proliferation in the hippocampus. Urothcarcinoma associated 1 (UCA1) is a long long non-coding RNA that was shown to regulate proliferation and differentiation of neural progenitors in vitro. We hypothesised that TLE-associated abnormal proliferation is a consequence of the downregulation of UCA1. This hypothesis was tested in mice with kainic acid (KA)-induced seizures, and then the potential mechanism was explored in vitro and in vivo. Result showed that the expression of UCA1 and Secreted Frizzled Related Protein 1 (SFRP1) were significantly reduced in hippocampal tissues of epileptic mice, while miR-375 was increased compared with the control group. Pearson correlation analysis showed that UCA1 was positively correlated with SFRP1, while miR-375 was negatively correlated with UCA1 and SFRP1. Besides, UCA1 was overexpressed in mice and the overexpression of UCA1 significantly reversed the abnormal proliferation of hippocampal neurons in epilepsy mice. In vitro Luciferase assay showed that UCA1 and Sfrp1 are both the targets of miR-375, and UCA1 promotes the expression of Sfrp1 by competitively adsorbing miR-375, thereby inhibiting the activation of the WNT/β-catenin pathway. The inactivation of the WNT/β-catenin pathway prevented the abnormal proliferation of neural progenitors in the epileptic hippocampus. In conclusion, our findings provide a theoretical basis for the clinical application of UCA1.

scholarly journals The Role of PHF19 As a Promoter of Tumorigenicity and Therapeutic Target in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 508-508
Author(s):  
Carolina D. Schinke ◽  
Pingping Qu ◽  
Shmuel Yaccoby ◽  
Valeriy V Lyzogubov ◽  
Veronica MacLeod ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Candidate Gene ◽  
Cell Lines ◽  
Crucial Role ◽  
Plasma Cells ◽  
Total Therapy

Introduction - Multiple Myeloma (MM) is a hematologic malignancy characterized by clonal growth of differentiated plasma cells (PCs). Despite improvement in MM therapy, the disease remains mostly incurable and is characterized by recurrent relapses with development of resistant clones that eventually lead to patient death. The pathways that lead to resistant and aggressive MM are not fully understood highlighting the need to improve our understanding of MM biology to identify potential new pathways and therapeutical targets. PHD Finger Protein 19 (PHF19) is a regulator of Polycomb Repressive Complex 2 (PRC2), the sole methyltransferase complex capable of catalyzing H3K27me3 to induce and enforce gene repression. PRC2 employs enhancer of zeste homolog 1 and 2 (EZH1/EZH2) as enzymatic subunits to hypermethylate H3K27. While overexpression and gain of function mutations of EZH1/2 have been observed in many cancers the role of this particular pathway in MM remains poorly understood. In the present study, we report on PHF19 as a new candidate gene to play a potential crucial role in MM oncogenesis. Methods- Gene expression profiling (GEP; Affymetrix U133 Plus 2.0) was performed on 739 MM patients (from total therapy trials [TT] 3-5; low risk MM n=636, high risk MM n=103), 42 patients with monoclonal gammopathy of undetermined significance (MGUS), 73 smoldering MM patients, 42 patients with primary plasma cell leukemia and 34 healthy donors. Myeloma risk was determined by the GEP 70 signature as previously defined. To test the implications of functional PHF19 knock down (KD) we used TRIPZ inducible PHF19 shRNA vs. scrambled control (Dharmacon) in two MM cell lines (JJN3 and ARP1). Real time PCR as well as western blotting was used to confirm PHF19 KD as well as to elucidate the effect on H3K27me3 (Cell Signaling). Functional in vitro studies included proliferation (Promega), clonogenic assays (StemCell), cell cycle and apoptosis assays (both Invitrogen). In vivo studies were performed using SCID mice that were subjected to tail vain injection with PHF19 KD JJN3 cells (n=10) or scrambled shRNA control (n=10). Weekly ELISA (Bethyl) and in vivo imaging (Xenogen) were performed and survival was recorded. Results- GEP of the previously mentioned patient populations and healthy controls identified PHF19 (chr9q33.2) as a candidate gene that was consistently dysregulated in MM patients. Mean expression levels at different MM stages correlated with disease aggressiveness (ANOVA, p<0.0001), Figure 1. High expression of PHF19 (log2>10.46) at diagnosis correlated significantly with adverse clinical parameters, including ISS III, anemia and elevated LDH, as well as worse overall survival (5 yr OS = 29% for patients with high PHF19 expression vs 77% for patients with low PHF19 expression [log2<10.46], p< 0.0001). These results led us to test the implications of functional PHF19 KD using TRIPZ inducible PHF19 shRNA vs. scrambled control in the JJN3 and ARP1 MM cell lines. PHF19 KD led to a drastic reduction of H3K27me3 thereby resulting in significantly reduced proliferation via cell cycle arrest, while apoptosis was not substantially altered. Clonogenic assays showed a significant reduction in colony numbers and size of MM cells with PHF19 KD compared to the control (>75% reduction in both cell lines, p<0.05). Xenograft studies showed consistently less tumor burden in the mice injected with PHF19 KD cells compared to scrambled control, evident through ELISA testing for IgG Kappa (Median =180 mg/ml for scrambled control vs 80 mg/ml for PHF19 KD at week 8, p=0.07) and bioimaging (Median bioilumisence 2.1x108 p/s for scrambled control vs. 0.8x108 p/s for PHF19 KD at week 8, non-significant). Median OS in mice injected with PHF19 KD cell was substantially longer (66 days) compared to mice subjected to scrambled control cells (54 days), p=0.052. Conclusion- In summary we show that PHF19 is upregulated in malignant plasma cells of MM patients and that PHF19 expression levels increase with advanced MM stages. High PHF19 expression was a marker of adverse prognosis in our total therapy (TT 3-5) cohort. Most importantly, in-vitro and in-vivo functional studies showed that PHF19 has important biological functions in MM. These results suggest that epigenetic regulation through histone methylation, in particular, H3K27 trimethylation, plays a crucial role in MM and the affected downstream pathways should be further elucidated. Disclosures Boyle: Janssen: Honoraria, Other: Travel; Abbvie: Honoraria; Amgen: Honoraria, Other: travel; Takeda: Honoraria, Other: travel; Celgene Corporation: Honoraria, Other: Travel. van Rhee:Kite Pharma: Consultancy; Adicet Bio: Consultancy; Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy; Castleman Disease Collaborative Network: Consultancy; EUSA: Consultancy. Walker:Celgene: Research Funding.

scholarly journals Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

2010 ◽  
Vol 316 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
Noriyuki Kioka ◽  
Takuya Ito ◽  
Hiroshi Yamashita ◽  
Natsuko Uekawa ◽  
Tsutomu Umemoto ◽  
...  
Keyword(s):  
Wound Healing ◽  
Crucial Role ◽  
Keratinocyte Migration

The role of NLRP3 inflammasome activation in the neuroinflammatory responses to Ag2Se quantum dots in microglia

Nanoscale ◽  
2019 ◽  
Vol 11 (43) ◽  
pp. 20820-20836 ◽  
Author(s):  
Tianshu Wu ◽  
Xue Liang ◽  
Keyu He ◽  
Tingting Wei ◽  
Yan Wang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Cytokine ◽  
Inflammasome Activation ◽  
Activated Microglia ◽  
Nlrp3 Inflammasome Activation

Ag2Se QD exposure activated microglia followed by pro-inflammatory cytokine IL-1β release in vivo and in vitro through NLRP3 inflammasome activation.

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