scholarly journals Combination of Peroxisome Proliferator-Activated Receptor (PPAR) Alpha and Gamma Agonists Prevents Corneal Inflammation and Neovascularization in a Rat Alkali Burn Model

2020 ◽  
Vol 21 (14) ◽  
pp. 5093
Author(s):  
Yuji Nakano ◽  
Takeshi Arima ◽  
Yutaro Tobita ◽  
Masaaki Uchiyama ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Inflammatory Cells ◽  
Vehicle Group ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alkali Burn ◽  
Pparγ Agonist ◽  
Pparγ Agonists

Peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) agonists have anti-inflammatory and anti-neovascularization effects, but few reports have tested the combination of PPARα and PPARγ agonists. In this study, we investigated the therapeutic effects of ophthalmic solutions of agonists of PPARα, PPARγ, and the combination in a rat corneal alkali burn model. After alkali injury, an ophthalmic solution of 0.05% fenofibrate (PPARα group), 0.1% pioglitazone (PPARγ group), 0.05% fenofibrate + 0.1% pioglitazone (PPARα+γ group), or vehicle (vehicle group) was topically instilled onto the rat’s cornea twice a day. After instillation, upregulation was seen of PPAR mRNA corresponding to each agonist group. Administration of agonists for PPARα, PPARγ, and PPARα+γ suppressed inflammatory cells, neovascularization, and fibrotic changes. In addition, the PPARγ agonist upregulated M2 macrophages, which contributed to wound healing, whereas the PPARα agonist suppressed immature blood vessels in the early phase. Administration of PPARα+γ agonists showed therapeutic effects in corneal wound healing, combining the characteristics of both PPARα and PPARγ agonists. The results indicate that the combination of PPARα and γ agonists may be a new therapeutic strategy.

scholarly journals Effects of Selective Peroxisome Proliferator Activated Receptor Agonists on Corneal Epithelial Wound Healing

2021 ◽  
Vol 14 (2) ◽  
pp. 88
Author(s):  
Yutaro Tobita ◽  
Takeshi Arima ◽  
Yuji Nakano ◽  
Masaaki Uchiyama ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Vehicle Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Corneal Epithelial ◽  
Ppar Agonist ◽  
Alkali Burn ◽  
Epithelial Wound Healing ◽  
Epithelial Healing

The effects of each subtype-selective peroxisome proliferator activated receptor (PPAR) agonist (α, β/δ, γ) on corneal epithelial wound healing were investigated using a rat corneal alkali burn model. After the alkali burn, each PPAR agonist or vehicle ophthalmic solution was instilled topically onto the rat’s cornea. Corneal epithelial healing processes were evaluated by fluorescein staining. Pathological analyses and real-time reverse transcription polymerase chain reactions were performed to evaluate Ki67 (proliferative maker) expression and inflammatory findings. The area of the corneal epithelial defect at 12 h and 24 h after the alkali burn was significantly smaller in each PPAR group than in the vehicle group. Ki67 mRNA expression was increased in the PPARβ/δ group, whereas mRNA expressions of inflammatory cytokines were suppressed in all of the PPAR agonist groups. Nuclear factor kappa B (NF-κB) was the most suppressed in the PPARγ group. The accelerated corneal epithelial healing effects of each PPAR ligand were thought to be related to the promotion of proliferative capacity and inhibition of inflammation.

scholarly journals Effects of peroxisome proliferator activated receptor gamma (PPARɣ) agonist on fasting model applied neuron cultures

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Arzu Pınarbaşı ◽  
Meltem Pak ◽  
Murat Kolay ◽  
Devrim Öz Arslan ◽  
Fehime Benli Aksungar
Keyword(s):  
Neurodegenerative Diseases ◽  
Citrate Synthase ◽  
Neuronal Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lactate Dehydrogenase Activity ◽  
Energy Metabolites ◽  
Pparγ Agonist ◽  
Mitochondrial Functions ◽  
Pparγ Agonists

Abstract Objectives Peroxisome proliferator activated receptor gamma (PPARγ) agonists used for the treatment of Diabetes Mellitus (DM), has important roles on the regulation of metabolism including ketogenesis in fasting and low glucose states. Recently PPARγ was proven to have anti-oxidant and anti-inflammatory effects on neuronal cells. Methods In the present study, effects of pioglitazone (PPARγ agonist) on cell survival, energy metabolism and mitochondrial functions were investigated in glucose deprived fasting model applied SH-SY5Y (ATCC/CRL 2266) cell lines. Before and after pioglitazone treatment; energy metabolites (glucose, lactate, ketone (βOHB), lactate dehydrogenase activity), mitochondrial citrate synthase activity and cell viability were investigated. Results and Conclusions PPARγ agonist addition to glucose deprived, ketone added neurons provided positive improvements in energy metabolites (p<0.01), mitochondrial functions (p<0.001) and survival rates (p<0.01). Changes in mitochondrial citrate synthase activity, lactate and LDH levels of neuronal cells treated with PPARγ agonist have not been previously shown. Our results suggest, pioglitazone as an effective alternative for the treatment of neurodegenerative diseases especially with the presence of ketone bodies. By clarifying the mechanisms of PPARγ agonists, a great contribution will be made to the treatment of neurodegenerative diseases.

scholarly journals Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

2016 ◽  
Vol 84 (7) ◽  
pp. 1975-1985 ◽  
Author(s):  
Brahmchetna Bedi ◽  
Zhihong Yuan ◽  
Myungsoo Joo ◽  
Susu M. Zughaier ◽  
Joanna B. Goldberg ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Nuclear Hormone Receptor ◽  
Host Cells ◽  
Peroxisome Proliferator ◽  
Bacterial Killing ◽  
Peroxisome Proliferator Activated Receptor ◽  
Content Type ◽  
Homoserine Lactones ◽  
Pparγ Agonist ◽  
Pparγ Agonists

The pathogenic profile ofPseudomonas aeruginosais related to its ability to secrete a variety of virulence factors. Quorum sensing (QS) is a mechanism wherein small diffusible molecules, specifically acyl-homoserine lactones, are produced byP. aeruginosato promote virulence. We show here that macrophage clearance ofP. aeruginosa(PAO1) is enhanced by activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). Macrophages treated with a PPARγ agonist (pioglitazone) showed enhanced phagocytosis and bacterial killing of PAO1. It is known that PAO1 QS molecules are inactivated by PON-2. QS molecules are also known to inhibit activation of PPARγ by competitively binding PPARγ receptors. In accord with this observation, we found that infection of macrophages with PAO1 inhibited expression of PPARγ and PON-2. Mechanistically, we show that PPARγ induces macrophage paraoxonase 2 (PON-2), an enzyme that degrades QS molecules produced byP. aeruginosa. Gene silencing studies confirmed that enhanced clearance of PAO1 in macrophages by PPARγ is PON-2 dependent. Further, we show that PPARγ agonists also enhance clearance ofP. aeruginosafrom lungs of mice infected with PAO1. Together, these data demonstrate thatP. aeruginosaimpairs the ability of host cells to mount an immune response by inhibiting PPARγ through secretion of QS molecules. These studies define a novel mechanism by which PPARγ contributes to the host immunoprotective effects during bacterial infection and suggest a role for PPARγ immunotherapy forP. aeruginosainfections.

scholarly journals Activation of Peroxisome Proliferator-activated Receptor α (PPARα) Suppresses Hypoxia-inducible Factor-1α (HIF-1α) Signaling in Cancer Cells

2012 ◽  
Vol 287 (42) ◽  
pp. 35161-35169 ◽  
Author(s):  
Jundong Zhou ◽  
Shuyu Zhang ◽  
Jing Xue ◽  
Jori Avery ◽  
Jinchang Wu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Proteasome Inhibitors ◽  
Tube Formation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Properties ◽  
Pparγ Agonist ◽  
Expression And Activity

Activation of peroxisome proliferator-activated receptor α (PPARα) has been demonstrated to inhibit tumor growth and angiogenesis, yet the mechanisms behind these actions remain to be characterized. In this study, we examined the effects of PPARα activation on the hypoxia-inducible factor-1α (HIF-1α) signaling pathway in human breast (MCF-7) and ovarian (A2780) cancer cells under hypoxia. Incubation of cancer cells under 1% oxygen for 16 h significantly induced HIF-1α expression and activity as assayed by Western blotting and reporter gene analysis. Treatment of the cells with PPARα agonists, but not a PPARγ agonist, prior to hypoxia diminished hypoxia-induced HIF-1α expression and activity, and addition of a PPARα antagonist attenuated the suppression of HIF-1α signaling. Activation of PPARα attenuated hypoxia-induced HA-tagged HIF-1α protein expression without affecting the HA-tagged HIF-1α mutant protein level, indicating that PPARα activation promotes HIF-1α degradation in these cells. This was further confirmed using proteasome inhibitors, which reversed PPARα-mediated suppression of HIF-1α expression under hypoxia. Using the co-immunoprecipitation technique, we found that activation of PPARα enhances the binding of HIF-1α to von Hippel-Lindau tumor suppressor (pVHL), a protein known to mediate HIF-1α degradation through the ubiquitin-proteasome pathway. Following PPARα-mediated suppression of HIF-1α signaling, VEGF secretion from the cancer cells was significantly reduced, and tube formation by endothelial cells was dramatically impaired. Taken together, these findings demonstrate for the first time that activation of PPARα suppresses hypoxia-induced HIF-1α signaling in cancer cells, providing novel insight into the anticancer properties of PPARα agonists.

scholarly journals PPARγ and TGFβ—Major Regulators of Metabolism, Inflammation, and Fibrosis in the Lungs and Kidneys

2021 ◽  
Vol 22 (19) ◽  
pp. 10431
Author(s):  
Gábor Kökény ◽  
Laurent Calvier ◽  
Georg Hansmann
Keyword(s):  
Transforming Growth Factor Beta ◽  
Kidney Failure ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Critical Conditions ◽  
Peroxisome Proliferator ◽  
Lipid Uptake ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

Peroxisome proliferator-activated receptor gamma (PPARγ) is a type II nuclear receptor, initially recognized in adipose tissue for its role in fatty acid storage and glucose metabolism. It promotes lipid uptake and adipogenesis by increasing insulin sensitivity and adiponectin release. Later, PPARγ was implicated in cardiac development and in critical conditions such as pulmonary arterial hypertension (PAH) and kidney failure. Recently, a cluster of different papers linked PPARγ signaling with another superfamily, the transforming growth factor beta (TGFβ), and its receptors, all of which play a major role in PAH and kidney failure. TGFβ is a multifunctional cytokine that drives inflammation, fibrosis, and cell differentiation while PPARγ activation reverses these adverse events in many models. Such opposite biological effects emphasize the delicate balance and complex crosstalk between PPARγ and TGFβ. Based on solid experimental and clinical evidence, the present review summarizes connections and their implications for PAH and kidney failure, highlighting the similarities and differences between lung and kidney mechanisms as well as discussing the therapeutic potential of PPARγ agonist pioglitazone.

scholarly journals Diet-dependent Natriuretic Peptide Receptor C expression in adipose tissue is mediated by PPARγ via long-range distal enhancers

2021 ◽  
Author(s):  
Fubiao Shi ◽  
Zoltan Simandi ◽  
Laszlo Nagy ◽  
Sheila Collins
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Long Range ◽  
Environmental Changes ◽  
Peroxisome Proliferator ◽  
Enhancer Activity ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Mouse Adipocytes ◽  
Sirna Knockdown

AbstractIn addition to their established role to maintain blood pressure and fluid volume, the cardiac natriuretic peptides (NPs) can stimulate adipocyte lipolysis and control the brown fat gene program of nonshivering thermogenesis. The NP “clearance” receptor C (NPRC) functions to clear NPs from the circulation via peptide internalization and degradation and thus is an important regulator of NP signaling and adipocyte metabolism. It is well appreciated that the Nprc gene is highly expressed in adipose tissue and is dynamically regulated with nutrition and environmental changes. However, the molecular basis for how Nprc gene expression is regulated is still poorly understood. Here we identified Peroxisome Proliferator-Activated Receptor gamma (PPARγ) as a transcriptional regulator of Nprc expression in mouse adipocytes. During 3T3-L1 adipocyte differentiation, levels of Nprc expression increase in parallel with PPARγ induction. Rosiglitazone, a classic PPARγ agonist, increases, while siRNA knockdown of PPARγ reduces, Nprc expression in 3T3-L1 adipocytes. We demonstrate that PPARγ controls Nprc gene expression in adipocytes through its long-range distal enhancers. Furthermore, the induction of Nprc expression in adipose tissue during high-fat diet feeding is associated with increased PPARγ enhancer activity. Our findings define PPARγ as a mediator of adipocyte Nprc gene expression and establish a new connection between PPARγ and the control of adipocyte NP signaling in obesity.

Sex hormones influence expression and function of peroxisome proliferator-activated receptor γ in adipocytes: pathophysiological aspects

2014 ◽  
Vol 20 (2) ◽  
Author(s):  
Hiromi Sato ◽  
Momoko Ishikawa ◽  
Hana Sugai ◽  
Asami Funaki ◽  
Yuki Kimura ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Metabolic Diseases ◽  
Fat Distribution ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Metabolic Homeostasis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Post Menopausal ◽  
And Function

AbstractAdipose tissue plays important roles not only in storing fat but also in maintaining metabolic homeostasis by regulating hundreds of biological signaling events and the secretion of various cytokines. One of the central regulators of adipocyte differentiation is peroxisome proliferator-activated receptor γ (PPARγ), which promotes downstream transcriptional activities, such as adiponectin. Disruption of homeostasis leads to the onset of metabolic diseases such as type 2 diabetes and other triggers for metabolic syndrome. Males and post-menopausal females are more likely to be affected with metabolic diseases than pre-menopausal females, suggesting that sex hormones might be involved in the pathogenesis and development of metabolic diseases. Indeed, 17β-estradiol, testosterone, dihydrotestosterone, and their receptors clearly play a role in adipose regulation: they can alter fat distribution and can modify the expression and activities of PPARγ and its downstream adipocytokines. Furthermore, sex hormones affect inflammatory factors such as nitric oxygen, nitric oxygen synthase, and their surrounding components. Sex hormones are also suggested to be involved with sex differences in the efficacy of the PPARγ agonist thiazolidinediones. Therefore, thorough investigation of how sex hormone-dependent regulation of metabolic homeostasis occurs is necessary in order to develop individualized clinical therapies optimized with regard to each patient’s biological condition and drug sensitivities.

15-Deoxy-Δ12,14-prostaglandin J2 and peroxisome proliferator-activated receptor γ (PPARγ) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARγ agonist on nitridergic and lipid placental metabolism

2005 ◽  
Vol 17 (4) ◽  
pp. 423 ◽  
Author(s):  
E. Capobianco ◽  
A. Jawerbaum ◽  
M. C. Romanini ◽  
V. White ◽  
C. Pustovrh ◽  
...  
Keyword(s):  
De Novo ◽  
Lipid Synthesis ◽  
Diabetic Rats ◽  
Lipid Homeostasis ◽  
Diabetic Rat ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Prostaglandin J2

15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor γ (PPARγ) ligand that regulates lipid homeostasis and has anti-inflammatory properties in many cell types. We postulated that 15dPGJ2 may regulate lipid homeostasis and nitric oxide (NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes-induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin-induced diabetic rats, 15dPGJ2 concentrations were decreased (83%) and immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/nitrites (an index of NO production) were diminished (40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPARγ activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of 14C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPARγ activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPARγ. We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPARγ were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.

Sign in / Sign up

Export Citation Format

Share Document