scholarly journals Analysis of PPARγ Signaling Activity in Psoriasis

2021 ◽  
Vol 22 (16) ◽  
pp. 8603
Author(s):  
Vladimir Sobolev ◽  
Anastasia Nesterova ◽  
Anna Soboleva ◽  
Alexandre Mezentsev ◽  
Evgenia Dvoriankova ◽  
...  
Keyword(s):  
T Cells ◽  
Laser Treatment ◽  
Psoriatic Skin ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Of Genes ◽  
Before And After ◽  
Low Levels ◽  
Pparγ Expression ◽  
Psoriatic Lesions

In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.

scholarly journals THE MODEL OF PPARγ DOWNREGULATED SIGNALING IN PSORIASIS

2020 ◽  
Author(s):  
Vladimir Sobolev ◽  
Anastasia Nesterova ◽  
Anna Soboleva ◽  
Evgenia Dvoriankova ◽  
Anastas Piruzyan ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
Nuclear Receptor ◽  
Psoriatic Skin ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Low Levels ◽  
Psoriasis Lesion ◽  
Psoriatic Lesions

ABSTRACTInteractions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin are correlated with the level of PPARγ expression and they belong to the same signaling pathway that regulates the development of psoriasis lesion.

scholarly journals The Model of PPARγ-Downregulated Signaling in Psoriasis

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Vladimir Sobolev ◽  
Anastasia Nesterova ◽  
Anna Soboleva ◽  
Evgenia Dvoriankova ◽  
Anastas Piruzyan ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
Nuclear Receptor ◽  
Psoriatic Skin ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Low Levels ◽  
Psoriasis Lesion ◽  
Psoriatic Lesions

Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ-downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin is correlated with the level of PPARγ expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

scholarly journals Growth Hormone Inhibits Apoptosis in Human Colonic Cancer Cell Lines: Antagonistic Effects of Peroxisome Proliferator Activated Receptor-γ Ligands

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3353-3362 ◽  
Author(s):  
Fausto Bogazzi ◽  
Federica Ultimieri ◽  
Francesco Raggi ◽  
Dania Russo ◽  
Renato Vanacore ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Colonic Cancer ◽  
Cancer Cell Lines ◽  
Peroxisome Proliferator ◽  
Signal Transducer ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antiapoptotic Effect ◽  
Pparγ Expression ◽  
Colonic Cells

Abstract GH has antiapoptotic effects on several cells. However, the antiapoptotic mechanisms of GH on colonic mucosa cells are not completely understood. Peroxisome proliferator activated receptor-γ (PPARγ) activation enhances apoptosis, and a link between GH and PPARγ in the colonic epithelium of acromegalic patients has been suggested. We investigated the effects of GH and of PPARγ ligands on apoptosis in colonic cancer cell lines. Colonic cells showed specific binding sites for GH, and after exposure to 0.05–50 nm GH, their apoptosis reduced by 45%. The antiapoptotic effect was due to either GH directly or GH-dependent local production of IGF-1. A 55–85% reduction of PPARγ expression was observed in GH-treated cells, compared with controls (P < 0.05). However, treatment of the cells with 1–50 μm ciglitazone (cig), induced apoptosis and reverted the antiapoptotic effects of GH by increasing the programmed cell death up to 3.5-fold at 30 min and up to 1.7-fold at 24 h. Expression of Bcl-2 and TNF-related apoptosis-induced ligand was not affected by either GH or cig treatment, whereas GH reduced the expression of Bax, which was increased by cig treatment. In addition, GH increased the expression of signal transducer and activator of transcription 5b, which might be involved in the down-regulation of PPARγ expression. In conclusion, GH may exert a direct antiapoptotic effect on colonic cells, through an increased expression of signal transducer and activator of transcription 5b and a reduction of Bax and PPARγ. The reduced GH-dependent apoptosis can be overcome by PPARγ ligands, which might be useful chemopreventive agents in acromegalic patients, who have an increased colonic polyps prevalence.

scholarly journals Peroxisome proliferator–activated receptor (PPAR)α expression in T cells mediates gender differences in development of T cell–mediated autoimmunity

2007 ◽  
Vol 176 (4) ◽  
pp. i9-i9
Author(s):  
Shannon E. Dunn ◽  
Shalina S. Ousman ◽  
Raymond A. Sobel ◽  
Luis Zuniga ◽  
Sergio E. Baranzini ◽  
...  
Keyword(s):  
Gender Differences ◽  
T Cells ◽  
T Cell ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Effects of 7°C environmental temperature acclimation during a 3-week training period

2020 ◽  
Vol 128 (4) ◽  
pp. 768-777
Author(s):  
Robert Shute ◽  
Katherine Marshall ◽  
Megan Opichka ◽  
Halee Schnitzler ◽  
Brent Ruby ◽  
...  
Keyword(s):  
Room Temperature ◽  
Environmental Temperature ◽  
Cellular Signaling ◽  
Temperature Acclimation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Training Adaptations ◽  
Before And After ◽  
The Impact ◽  
Environmental Temperatures

Cold environmental temperatures during exercise and recovery alter the acute response to cellular signaling and training adaptations. Approximately 3 wk is required for cold temperature acclimation to occur. To determine the impact of cold environmental temperature on training adaptations, fitness measurements, and aerobic performance, two groups of 12 untrained male subjects completed 1 h of cycling in 16 temperature acclimation sessions in either a 7°C or 20°C environmental temperature. Fitness assessments before and after acclimation occurred at standard room temperature. Muscle biopsies were taken from the vastus lateralis muscle before and after training to assess molecular markers related to mitochondrial development. Peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1α) mRNA was higher in 7°C than in 20°C in response to acute exercise before training ( P = 0.012) but not after training ( P = 0.813). PGC-1α mRNA was lower after training ( P < 0.001). BNIP3 was lower after training in the 7°C than in the 20°C group ( P = 0.017) but not before training ( P = 0.549). No other differences occurred between temperature groups in VEGF, ERRα, NRF1, NRF2, TFAM, PINK1, Parkin, or BNIP3L mRNAs ( P > 0.05). PGC-1α protein and mtDNA were not different before training, after training, or between temperatures ( P > 0.05). Cycling power increased during the daily training ( P < 0.001) but was not different between temperatures ( P = 0.169). V̇o2peak increased with training ( P < 0.001) but was not different between temperature groups ( P = 0.460). These data indicate that a 3-wk period of acclimation/training in cold environmental temperatures alters PGC-1α gene expression acutely but this difference is not manifested in a greater increase in V̇o2peak and is dissipated as acclimation takes place. NEW & NOTEWORTHY This study examines the adaptive response of cellular signaling during exercise in cold environmental temperatures. We demonstrate that peroxisome proliferator-activated receptor-γ coactivator 1α mRNA is different between cold and room temperature environments before training but after training this difference no longer exists. This initial difference in transcriptional response between temperatures does not lead to differences in performance measures or increases in protein or mitochondria.

scholarly journals Central leptin regulates heart lipid content by selectively increasing PPAR β/δ expression

2018 ◽  
Vol 236 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Cristina Mora ◽  
Cristina Pintado ◽  
Blanca Rubio ◽  
Lorena Mazuecos ◽  
Virginia López ◽  
...  
Keyword(s):  
Target Genes ◽  
Cardiac Tissue ◽  
Cardiac Metabolism ◽  
Pyruvate Dehydrogenase Kinase ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Of Genes ◽  
Gene And Protein Expression ◽  
Tag Accumulation

The role of central leptin in regulating the heart from lipid accumulation in lean leptin-sensitive animals has not been fully elucidated. Herein, we investigated the effects of central leptin infusion on the expression of genes involved in cardiac metabolism and its role in the control of myocardial triacylglyceride (TAG) accumulation in adult Wistar rats. Intracerebroventricular (icv) leptin infusion (0.2 µg/day) for 7 days markedly decreased TAG levels in cardiac tissue. Remarkably, the cardiac anti-steatotic effects of central leptin were associated with the selective upregulation of gene and protein expression of peroxisome proliferator-activated receptor β/δ (PPARβ/δ, encoded by Pparb/d) and their target genes, adipose triglyceride lipase (encoded by Pnpla2, herefater referred to as Atgl), hormone sensitive lipase (encoded by Lipe, herefater referred to as Hsl), pyruvate dehydrogenase kinase 4 (Pdk4) and acyl CoA oxidase 1 (Acox1), involved in myocardial intracellular lipolysis and mitochondrial/peroxisomal fatty acid utilization. Besides, central leptin decreased the expression of stearoyl-CoA deaturase 1 (Scd1) and diacylglycerol acyltransferase 1 (Dgat1) involved in TAG synthesis and increased the CPT-1 independent palmitate oxidation, as an index of peroxisomal β-oxidation. Finally, the pharmacological inhibition of PPARβ/δ decreased the effects on gene expression and cardiac TAG content induced by leptin. These results indicate that leptin, acting at central level, regulates selectively the cardiac expression of PPARβ/δ, contributing in this way to regulate the cardiac TAG accumulation in rats, independently of its effects on body weight.

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