scholarly journals The Interplay of WNT and PPARγ Signaling in Vascular Calcification

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2658
Author(s):  
Stefan Reinhold ◽  
W. Matthijs Blankesteijn ◽  
Sébastien Foulquier
Keyword(s):  
Transcription Factor ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Vascular Calcification ◽  
Atherosclerotic Plaque ◽  
Direct Interaction ◽  
Cardiovascular Death ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Related Transcription Factor

Vascular calcification (VC), the ectopic deposition of calcium phosphate crystals in the vessel wall, is one of the primary contributors to cardiovascular death. The pathology of VC is determined by vascular topography, pre-existing diseases, and our genetic heritage. VC evolves from inflammation, mediated by macrophages, and from the osteochondrogenic transition of vascular smooth muscle cells (VSMC) in the atherosclerotic plaque. This pathologic transition partly resembles endochondral ossification, involving the chronologically ordered activation of the β-catenin-independent and -dependent Wingless and Int-1 (WNT) pathways and the termination of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction. Several atherosclerotic plaque studies confirmed the differential activity of PPARγ and the WNT signaling pathways in VC. Notably, the actively regulated β-catenin-dependent and -independent WNT signals increase the osteochondrogenic transformation of VSMC through the up-regulation of the osteochondrogenic transcription factors SRY-box transcription factor 9 (SOX9) and runt-related transcription factor 2 (RUNX2). In addition, we have reported studies showing that WNT signaling pathways may be antagonized by PPARγ activation via the expression of different families of WNT inhibitors and through its direct interaction with β-catenin. In this review, we summarize the existing knowledge on WNT and PPARγ signaling and their interplay during the osteochondrogenic differentiation of VSMC in VC. Finally, we discuss knowledge gaps on this interplay and its possible clinical impact.

scholarly journals Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Aaron W. James
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Adipogenic Differentiation ◽  
Cell Types ◽  
Bmp Signaling ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Growth Factor ◽  
Related Transcription Factor

Mesenchymal stem cells (MSC) are multipotent cells, functioning as precursors to a variety of cell types including adipocytes, osteoblasts, and chondrocytes. Between osteogenic and adipogenic lineage commitment and differentiation, a theoretical inverse relationship exists, such that differentiation towards an osteoblast phenotype occurs at the expense of an adipocytic phenotype. This balance is regulated by numerous, intersecting signaling pathways that converge on the regulation of two main transcription factors: peroxisome proliferator-activated receptor-γ(PPARγ) and Runt-related transcription factor 2 (Runx2). These two transcription factors, PPARγand Runx2, are generally regarded as the master regulators of adipogenesis and osteogenesis. This review will summarize signaling pathways that govern MSC fate towards osteogenic or adipocytic differentiation. A number of signaling pathways follow the inverse balance between osteogenic and adipogenic differentiation and are generally proosteogenic/antiadipogenic stimuli. These includeβ-catenin dependent Wnt signaling, Hedgehog signaling, and NELL-1 signaling. However, other signaling pathways exhibit more context-dependent effects on adipogenic and osteogenic differentiation. These include bone morphogenic protein (BMP) signaling and insulin growth factor (IGF) signaling, which display both proosteogenic and proadipogenic effects. In summary, understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.

scholarly journals RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome

2006 ◽  
Vol 154 (1) ◽  
pp. 159-166 ◽  
Author(s):  
M Messager ◽  
C Carrière ◽  
X Bertagna ◽  
Y de Keyzer
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Ectopic Acth Syndrome ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Ectopic Acth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carcinoid Tumours ◽  
Transcription Factor Genes

Objective: ACTH is frequently produced in non-pituitary tumours, leading to the ectopic-ACTH syndrome, but the molecular mechanisms of its expression remain obscure. This study was aimed at understanding the transcription mechanisms of the ACTH-precursor gene in carcinoid tumours of the lung or thymus. Design: Transcripts coding for a series of corticotroph-associated transcription factor genes were detected, together with markers of the corticotroph phenotype. We studied a series of 41 carcinoid tumours including 15 with proven ectopic-ACTH syndrome. Methods: Specific RT-PCR reactions were designed for each gene including alternatively spliced isoforms. Results: The markers of the corticotroph phenotype were detected in all ACTH-positive tumours. Expression of the Tpit and Pitx1 genes were not restricted to ACTH-positive tumours but were also detected in many ACTH-negative carcinoids. Only a subset of ACTH-negative tumours expressed NAK-1/Nur77, and NeuroD1 expression was detected in <50% of the tumours regardless of their secretory status. The glucocorticoid receptor alpha was detected in every tumour in contrast to its beta isoform detectable in a few tumours only. Chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and peroxisome proliferator-activated receptor (PPAR) γ2 were expressed in 50% of the tumours of each group whereas PPARγ1 was expressed in almost every tumour. Conclusions: ACTH-positive carcinoids do not share a characteristic expression pattern of the corticotroph-associated transcription factor genes, suggesting that the transcriptional mechanisms of the ACTH-precursor gene differ from those in normal pituitary corticotrophs. Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation.

scholarly journals High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δAgonism

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Elisa Benetti ◽  
Raffaella Mastrocola ◽  
Mara Rogazzo ◽  
Fausto Chiazza ◽  
Manuela Aragno ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Gastrocnemius Muscle ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Intercellular Adhesion Molecule ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Intercellular Adhesion Molecule 1 ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome Proliferator Activated Receptor (PPAR)-δagonists may serve for treating metabolic diseases. However, the effects of PPAR-δagonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δagonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δupregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δactivation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.

Glutaminase Affects the Transcriptional Activity of Peroxisome Proliferator-Activated Receptor γ (PPARγ) via Direct Interaction

Biochemistry ◽  
2018 ◽  
Vol 57 (44) ◽  
pp. 6293-6307 ◽  
Author(s):  
Carolina Aparecida de Guzzi Cassago ◽  
Marília Meira Dias ◽  
Matheus Pinto Pinheiro ◽  
Camila Cristina Pasquali ◽  
Alliny Cristiny Silva Bastos ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Direct Interaction ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 528 ◽  
Author(s):  
Ayman M. Mahmoud ◽  
Ekram M. Desouky ◽  
Walaa G. Hozayen ◽  
May Bin-Jumah ◽  
El-Shaymaa El-Nahass ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Signaling Pathways ◽  
Mesoporous Silica Nanoparticles ◽  
Kidney Injury ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Liver And Kidney

Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.

scholarly journals Screening of Prognostic Factors in Early-Onset Breast Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303381989367 ◽  
Author(s):  
Zhun Yu ◽  
Qi He ◽  
Guoping Xu
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Differentially Expressed Genes ◽  
Early Onset ◽  
Differentially Expressed ◽  
Peroxisome Proliferator ◽  
Early Onset Breast Cancer ◽  
Microrna Target ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Protein Interaction

Background: Gene expression profiles from early-onset breast cancer and normal tissues were analyzed to explore the genes and prognostic factors associated with breast cancer. Methods: GSE109169 and GSE89116 were obtained from the database of Gene Expression Omnibus. We firstly screened the differentially expressed genes between tumor samples and normal samples from patients with early-onset breast cancer. Based on database for annotation, visualization and intergrated discovery (DAVID) tool, functional analysis was calculated. Transcription factor-target regulation and microRNA-target gene network were constructed using the tool of transcriptional regulatory relatitionships unraveled by sentence-based text mining (TRRUST) and miRWalk2.0, respectively. The prognosis-related survival information was compiled based on The Cancer Genome Atlas breast cancer clinical data. Results: A total of 708 differentially expressed genes from GSE109169 data sets and 358 differentially expressed genes from GSE89116 data sets were obtained, of which 122 common differentially expressed genes including 102 uniformly downregulated genes and 20 uniformly upregulated genes were screened. Protein–protein interaction network with a total of 83 nodes and 157 relationship pairs was obtained, and genes in protein–protein interaction, such as peroxisome proliferator-activated receptor γ, FGF2, adiponectin, and PCK1, were recognized as key nodes in protein–protein interaction. In total, 66 transcription factor–target relationship pairs were obtained, and peroxisome proliferator-activated receptor γ was the only one downregulated transcription factor. MicroRNA-target gene network contained 368 microRNA-target relationship pairs. Moreover, 16 differentially expressed genes, including 2 upregulations and 14 downregulations, were related to a significant correlation with the prognosis, including SQLE and peroxisome proliferator-activated receptor γ. Conclusions: SQLE and peroxisome proliferator-activated receptor γ might be important prognostic factors in breast cancers, and adiponectin might be important in breast cancer pathogenesis regulated by peroxisome proliferator-activated receptor γ.

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