scholarly journals PPARγSignaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Virender K. Rehan ◽  
John S. Torday
Keyword(s):  
Evolutionary Biology ◽  
Atmospheric Oxygen ◽  
Alveolar Type ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lung Physiology ◽  
Parathyroid Hormone Related Protein ◽  
Health And Disease ◽  
Pathogenic Agents ◽  
Pparγ Expression

Epithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyroid-hormone-related protein, and its binding to its receptor on the mesenchyme, inducing PPARγ expression by lipofibroblasts. Lipofibroblasts then produce leptin, which binds to alveolar type II cells, stimulating their production of surfactant, which is necessary for both evolutionary and physiologic adaptation to atmospheric oxygen from fish to man. A wide variety of molecular insults disrupt such highly evolved physiologic cell-cell interactions, ranging from overdistention to oxidants, infection, and nicotine, all of which predictably cause loss of mesenchymal peroxisome-proliferator-activated receptor gamma (PPARγ) expression and the transdifferentiation of lipofibroblasts to myofibroblasts, the signature cell type for lung fibrosis. By exploiting such deep cell-molecular functional homologies as targets for leveraging lung homeostasis, we have discovered that we can effectively prevent and/or reverse the deleterious effects of these pathogenic agents, demonstrating the utility of evolutionary biology for the prevention and treatment of chronic lung disease. By understanding mechanisms of health and disease as an evolutionary continuum rather than as dissociated processes, we can evolve predictive medicine.

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 PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

scholarly journals How Epigenetic Modifications Drive the Expression and Mediate the Action of PGC-1α in the Regulation of Metabolism

2019 ◽  
Vol 20 (21) ◽  
pp. 5449 ◽  
Author(s):  
Anne I. Krämer ◽  
Christoph Handschin
Keyword(s):  
Current Knowledge ◽  
Transcriptional Networks ◽  
Peroxisome Proliferator ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Regulation Of Metabolism ◽  
Health And Disease ◽  
Short And Long Term

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

scholarly journals Prostanoid EP4 agonist L-902,688 activates PPARγ and attenuates pulmonary arterial hypertension

2018 ◽  
Vol 314 (3) ◽  
pp. L349-L359 ◽  
Author(s):  
Hsin-Hsien Li ◽  
Hsao-Hsun Hsu ◽  
Gwo-Jyh Chang ◽  
I-Chen Chen ◽  
Wan-Jing Ho ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Arterial Remodeling ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pulmonary Arterial ◽  
And Migration ◽  
Pparγ Expression

Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cAMP synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH), but this signaling may occur through nuclear peroxisome proliferator-activated receptor-γ (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activates signal transduction. We investigated the effect of an EP4-specific agonist on pulmonary arterial remodeling and its regulatory mechanisms in pulmonary arterial smooth muscle cells (PASMCs). Immunoblotting evealed IP, EP4, and PPARγ expression in human pulmonary arterial hypertension (PAH) and monocrotaline (MCT)-induced PAH rat lung tissue. Isolated PASMCs from MCT-induced PAH rats (MCT-PASMCs) were treated with L-902,688, a selective EP4 agonist, to investigate the anti-vascular remodeling effect. Scant expression of IP and PPARγ but stable expression of EP4 was observed in IPAH patient lung tissues and MCT-PASMCs. L-902,688 inhibited IP-insufficient MCT-PASMC proliferation and migration by activating PPARγ in a time- and dose-dependent manner, but these effects were reversed by AH-23848 (an EP4 antagonist) and H-89 [a protein kinase A (PKA) inhibitor], highlighting the crucial role of PPARγ in the activity of this EP4 agonist. L-902,688 attenuated pulmonary arterial remodeling in hypoxic PAH mice and MCT-induced PAH rats; therefore, we conclude that the selective EP4 agonist L-902,688 reverses vascular remodeling by activating PPARγ. This study identified a novel EP4-PKA-PPARγ pathway, and we propose EP4 as a potential therapeutic target for PAH.

scholarly journals Hepatic PPARγ Is Not Essential for the Rapid Development of Steatosis After Loss of Hepatic GH Signaling, in Adult Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1728-1735 ◽  
Author(s):  
Rhonda D. Kineman ◽  
Neena Majumdar ◽  
Papasani V. Subbaiah ◽  
Jose Cordoba-Chacon
Keyword(s):  
De Novo ◽  
Rapid Development ◽  
De Novo Lipogenesis ◽  
Peroxisome Proliferator ◽  
Male Mice ◽  
Double Knockout ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Expression ◽  
Triglyceride Content ◽  
Pparγ Expression

Abstract Our group has previously reported de novo lipogenesis (DNL) and hepatic triglyceride content increases in chow-fed male mice within 7 days of hepatocyte-specific GH receptor knockdown (aLivGHRkd). Here, we report that these changes are associated with an increase in hepatic expression of peroxisome proliferator-activated receptor γ (PPARγ), consistent with previous reports showing steatosis is associated with an increase in PPARγ expression in mice with congenital loss of hepatic GH signaling. PPARγ is thought to be an important driver of steatosis by enhancing DNL, as well as increasing the uptake and esterification of extrahepatic fatty acids (FAs). In order to determine whether hepatic PPARγ is critical for the rapid development of steatosis in the aLivGHRkd mouse model, we have generated aLivGHRkd mice, with or without PPARγ (ie, adult-onset, hepatocyte-specific double knockout of GHR and PPARγ). Hepatic PPARγ was not required for the rapid increase in liver triglyceride content or FA indexes of DNL (16:0/18:2 and 16:1/16:0). However, loss of hepatic PPARγ blunted the rise in fatty acid translocase/CD36 and monoacylglycerol acyltransferase 1 expression induced by aLivGHRkd, and this was associated with a reduction in the hepatic content of 18:2. These results suggest that the major role of PPARγ is to enhance pathways critical in uptake and reesterification of extrahepatic FA. Because FAs have been reported to directly increase PPARγ expression, we speculate that in the aLivGHRkd mouse, the FA produced by DNL enhances the expression of PPARγ, which in turn increases extrahepatic FA uptake, thereby further enhancing PPARγ activity and exacerbating steatosis overtime.

scholarly journals Increasing Fat Deposition via Upregulates the Transcription of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Native Crossbred Chicken

2020 ◽  
Author(s):  
Supanon Tunim ◽  
Yupin Phasuk ◽  
Samuel E. Aggrey ◽  
Monchai Duangjinda
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Intramuscular Fat ◽  
Abdominal Fat ◽  
Fat Deposition ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Chicken Breeds ◽  
Pparγ Expression ◽  
Pparγ Gene

Abstract Background: Crossbreeding using exotic breeds is usually employed to improve the growth characteristics of indigenous chickens. This mating not only provides growth but affect adversely to fat deposition as well. We studied the growth, abdominal, subcutaneous and intramuscular fat and mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and PPARγ in adipose and muscle tissues of four chicken breeds [Chee breed (CH) (100% Thai native chicken), Kaimook e-san1 (KM1; 50% CH background), Kaimook e-san2 (KM2; 25% CH background), and broiler (BR)]. This study was aim to study role of PPARs on fat deposition in native crossbred chicken.Results: The BR chickens had higher abdominal fat than other breeds (P<0.05) and the KM2 had an abdominal fat percentage higher than KM1 and CH respectively (P<0.05). The intramuscular fat (IMF) of BR was greater than KM1 and CH (P<0.05). In adipose tissue, PPARα transcription expression was different among the chicken breeds. However, there were breed differences in PPARγ gene expression. Study of abdominal fat PPARγ gene expression showed the BR breed, KM1, and KM2 breed significantly greater (P<0.05) than CH. In 8 to 12 weeks of age, the result shows that the PPARγ expression of the CH breed is less than (P<0.05) KM2. The result of PPARs expression in muscle tissue was similar result in adipose tissue.Conclusion: Crossbreeding improved the growth of the Thai native breed, there was also a corresponding increase in carcass fatness. However, there appears to be a relationship between PPARγ expression and fat deposition traits. therefore, PPARγ activity plays a key role in lipid accumulation by up-regulation.

scholarly journals Low-dose Bisphenol-A Promotes Epigenetic Changes at Pparγ Promoter in Adipose Precursor Cells

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3498
Author(s):  
Michele Longo ◽  
Federica Zatterale ◽  
Jamal Naderi ◽  
Cecilia Nigro ◽  
Francesco Oriente ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Promoter Methylation ◽  
Low Dose ◽  
Precursor Cells ◽  
Peroxisome Proliferator ◽  
Epigenetic Changes ◽  
Obesity Prevalence ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Expression

Exposure to endocrine-disrupting chemicals such as Bisphenol-A (BPA) is associated with an increase in obesity prevalence. Diet is the primary cause of human exposure to this contaminant. BPA promotes obesity by inducing adipocyte dysfunction and altering adipogenesis. Contradictory evidence and unanswered questions are reported in the literature concerning the BPA effects on adipogenesis. To clarify this issue, we tested the effects of prolonged low-dose BPA exposure on different phases of adipogenesis in committed 3T3L1 and uncommitted NIH3T3 preadipocytes. Our findings show that BPA effects on the adipogenesis are mediated by epigenetic mechanisms by reducing peroxisome proliferator-activated receptor gamma (Pparγ) promoter methylation in preadipocytes. Nevertheless, in BPA-exposed 3T3L1, Pparγ expression only transiently increases as lipid accumulation at day 4 of differentiation, without altering the adipogenic potential of the precursor cells. In the absence of differentiation mix, BPA does not make the 3T3L1 an in vitro model of spontaneous adipogenesis and the effects on the Pparγ expression are still limited at day 4 of differentiation. Furthermore, BPA exposure does not commit the NIH3T3 to the adipocyte lineage, although Pparγ overexpression is more evident both in preadipocytes and during the adipocyte differentiation. Interestingly, termination of the BPA exposure restores the Pparγ promoter methylation and inflammatory profile of the 3T3L1 cells. This study shows that BPA induces epigenetic changes in a key adipogenic gene. These modifications are reversible and do not affect preadipocyte commitment and/or differentiation. We identify an alternative transcriptional mechanism by which BPA affects gene expression and demonstrate how the challenge of preventing exposure is fundamental for human health.

scholarly journals Roles of NF-κB Activation and Peroxisome Proliferator-Activated Receptor Gamma Inhibition in the Effect of Rifampin on Inducible Nitric Oxide Synthase Transcription in Human Lung Epithelial Cells

2008 ◽  
Vol 53 (4) ◽  
pp. 1539-1545 ◽  
Author(s):  
Yael Yuhas ◽  
Eva Berent ◽  
Regev Cohen ◽  
Shai Ashkenazi
Keyword(s):  
Nitric Oxide ◽  
Human Lung ◽  
Inos Mrna ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Genes ◽  
Lung Epithelial ◽  
Pparγ Expression ◽  
Inducible Nitric Oxide

ABSTRACT Rifampin (rifampicin), an important antibiotic agent and a major drug used for the treatment of tuberculosis, exerts immunomodulatory effects. Previous studies have found that rifampin increases inducible nitric oxide (NO) synthase (iNOS) expression and NO production. The present study investigated the potential mechanism(s) underlying these actions. The incubation of human lung epithelial A549 cells with a cytokine mix (interleukin-1β, tumor necrosis factor alpha, and gamma interferon) induced the expression of iNOS mRNA. The addition of rifampin increased the iNOS level by 1.9 ± 0.3-fold at a dose of 10 μg/ml (P < 0.01) and by 4.0 ± 0.3-fold at a dose of 50 μg/ml (P < 0.001). Rifampin treatment also affected the transcription factors that regulate iNOS mRNA: there was an increased and prolonged degradation of the inhibitory subunit of NF-κB, a corresponding increase in the level of cytokine-induced DNA binding of NF-κB (2.1 ± 0.2-fold), and a decrease in the level of expression of peroxisome proliferator-activated receptor gamma (PPARγ). Specifically, the level of PPARγ expression dropped by 15% in response to cytokine stimulation and by an additional 40% when rifampin was added (P < 0.001). Rifampin had no effect on the activation of mitogen-activated protein kinases or the signal transducer and transcription activator (STAT-1). In conclusion, rifampin augments NO production by upregulating iNOS mRNA. It also increases the level of NF-κB activation and decreases the level of PPARγ expression. The increases in the levels of NF-κB activation and NO production probably contribute to the therapeutic effects of rifampin. However, given the role of NF-κB in upregulating many inflammatory genes and the roles of PPARγ in downregulating inflammatory genes and in lipid and glucose metabolism, these findings have implications for potential adverse effects of rifampin in patients with chronic inflammatory diseases and glucose or lipid disorders.

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