scholarly journals Short- and long-term impact of hyperoxia on the blood and retinal cells’ transcriptome in a mouse model of oxygen-induced retinopathy

2019 ◽  
Vol 87 (3) ◽  
pp. 485-493 ◽  
Author(s):  
Magdalena Zasada ◽  
Anna Madetko-Talowska ◽  
Cecilie Revhaug ◽  
Anne Gro W. Rognlien ◽  
Lars O. Baumbusch ◽  
...  

Abstract Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Author(s):  
Agata Krawczyk ◽  
Barbara Strzałka-Mrozik ◽  
Dominika Wcisło-Dziadecka ◽  
Magdalena Kimsa-Dudek ◽  
Celina Kruszniewska-Rajsa ◽  
...  

IntroductionThe primary goal of psoriasis treatment is to reduce the inflammatory response and associated complications. In severe cases of psoriasis that are resistant to local treatment (e.g., keratolytic preparations) and at least two types of general treatment methods (e.g., retinoids and cyclosporine A), biological therapy is used. This study aimed to assess the systemic effects of adalimumab at a given stage of treatment in patients with psoriatic arthritis and evaluate how the drug can improve the clinical condition of the patients.Material and methodsThe study group consisted of patients with diagnosed psoriatic arthritis, while the control group consisted of individuals from whom peripheral blood mononuclear cells were obtained. The effects of the administration of adalimumab were assessed by analyzing the gene expression using oligonucleotide microarrays.ResultsThe apoptosis process was indicated as one of the overrepresented categories (the PANTHER classification system 13.1 program, overrepresentativity test, p < 0.05). The dermatological indexes decreased, indicating an improvement in the clinical conditions of the patients three months after the first dose of adalimumab.ConclusionsWe found that adalimumab affects apoptosis, which is crucial in the development and course of psoriasis. The differential gene expression in peripheral blood mononuclear cells of patients with psoriatic arthritis indicated the potential systemic effects of adalimumab therapy. The analyses of dermatological (the Psoriasis Area And Severity Index, body surface area and Dermatology Life Quality Index) and inflammatory (Biernacki’s reaction) parameters revealed the effectiveness of the therapy.


2003 ◽  
Vol 71 (11) ◽  
pp. 6487-6498 ◽  
Author(s):  
Paul M. Coussens ◽  
Christopher J. Colvin ◽  
Guilherme J. M. Rosa ◽  
Juliana Perez Laspiur ◽  
Michael D. Elftman

ABSTRACT A bovine-specific cDNA microarray system was used to compare gene expression profiles of peripheral blood mononuclear cells (PBMCs) from control uninfected (n = 4) and Johne's disease-positive (n = 6) Holstein cows. Microarray experiments were designed so that for each animal, a direct comparison was made between PBMCs stimulated in vitro with Mycobacterium avium subsp. paratuberculosis and PBMCs stimulated with phosphate-buffered saline (nil-stimulated PBMCs). As expected, M. avium subsp. paratuberculosis stimulation of infected cow PBMCs enhanced expression of gamma interferon transcripts. In addition, expression of 15 other genes was significantly affected (>1.25-fold change; P < 0.05) by in vitro stimulation with M. avium subsp. paratuberculosis. Similar treatment of control cow PBMCs with M. avium subsp. paratuberculosis resulted in significant changes in expression of 13 genes, only 2 of which were also affected in PBMCs from the infected cow PBMCs. To compare gene expression patterns in the two cow infection groups (infected cows and uninfected cows), a mixed-model analysis was performed with the microarray data. This analysis indicated that there were major differences in the gene expression patterns between cells isolated from the two groups of cows, regardless of in vitro stimulation. A total of 86 genes were significantly differentially expressed (P < 0.01) in M. avium subsp. paratuberculosis-stimulated PBMCs from infected cows compared to expression in similarly treated PBMCs from control cows. Surprisingly, a larger number of genes (110 genes) were also found to be significantly differentially expressed (P < 0.01) in nil-stimulated cells from the two infection groups. The expression patterns of selected genes were substantiated by quantitative real-time reverse transcriptase PCR. Flow cytometric analysis indicated that there were no gross differences in the relative populations of major immune cell types in PBMCs from infected and control cows. Thus, data presented in this report indicate that the gene expression program of PBMCs from M. avium subsp. paratuberculosis-infected cows is inherently different from that of cells from control uninfected cows.


2011 ◽  
Vol 43 (10) ◽  
pp. 566-570 ◽  
Author(s):  
Tomoyuki Nakasa ◽  
Yoshihiko Nagata ◽  
Keiichiro Yamasaki ◽  
Mitsuo Ochi

MicroRNA (miRNA) is a class of noncoding RNA that exhibits tissue- or developmental stage-specific expression patterns and negatively regulates gene expression. MiRNAs play an important role in human diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). OA is characterized by the progressive destruction of articular cartilage, and several miRNAs exhibit altered expression, playing a role in regulating gene expression in OA pathogenesis, especially in catabolic factors such as matrix metalloproteinases (MMP) and aggrecanases. RA is an autoimmune disease that is characterized by irreversible joint destruction due to chronic synovial inflammation. MiRNAs play an important role in inflammatory response, synovial cell proliferation, and production of MMPs in RA synovial tissues. The expression level of several miRNAs in peripheral blood mononuclear cells correlates with RA disease activity. Recently, therapeutic trials aimed at targeting miRNA in vivo have been conducted. Targeting miRNA will enable a new advanced strategy toward arthritis treatment.


2008 ◽  
Vol 158 (4) ◽  
pp. 499-510 ◽  
Author(s):  
Ursula Mager ◽  
Marjukka Kolehmainen ◽  
Vanessa D F de Mello ◽  
Ursula Schwab ◽  
David E Laaksonen ◽  
...  

ObjectiveWe examined the expression of ghrelin and ghrelin receptors in peripheral blood mononuclear cells (PBMCs) and evaluated the effect of weight loss or exercise on plasma ghrelin concentrations in subjects with the metabolic syndrome.Design and methodsData from 75 overweight/obese subjects randomized to a weight loss, aerobic exercise, resistance exercise or control group for a 33-week intervention period were analysed. The plasma ghrelin concentrations and indices of insulin and glucose metabolism were assessed, and mRNA expression of ghrelin, its receptors and various cytokines in PBMCs was studied using real-time PCR.ResultsGhrelin and GH secretagogue receptor 1b were expressed in PBMCs of subjects with metabolic syndrome. Ghrelin gene expression correlated positively with the expressions of tumour necrosis factor-α (P<0.001), interleukin-1β (P<0.001) and interleukin-6 (P=0.026) during the study, but was not associated with the plasma ghrelin concentration. Genotype-specific ghrelin gene expression in PBMCs was found for the −604G/A and the −501A/C polymorphisms in the ghrelin gene. At baseline, the plasma ghrelin levels were associated with fasting serum insulin concentrations, insulin sensitivity index and high-density lipoprotein cholesterol. However, longitudinally weight, BMI or waist circumference and acute insulin response in i.v. glucose tolerance test were stronger predictors of the ghrelin concentration. Plasma ghrelin did not change over the study period in the weight reduction group, but it tended to decrease in the control group (P=0.050).ConclusionsGhrelin mRNA expression in PBMCs suggests an autocrine role for ghrelin within an immune microenvironment. Moderate long-term weight loss may prevent a decline in ghrelin concentration over time in individuals with metabolic syndrome.


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