scholarly journals Pemafibrate Prevents Retinal Pathological Neovascularization by Increasing FGF21 Level in a Murine Oxygen-Induced Retinopathy Model

2019 ◽  
Vol 20 (23) ◽  
pp. 5878 ◽  
Author(s):  
Yohei Tomita ◽  
Nobuhiro Ozawa ◽  
Yukihiro Miwa ◽  
Ayako Ishida ◽  
Masayuki Ohta ◽  
...  
Keyword(s):  
Growth Factor ◽  
Large Scale ◽  
Luciferase Assay ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Pathological Angiogenesis ◽  
Oxygen Induced Retinopathy

Large-scale clinical trials, such as the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies, have shown that the administration of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, suppresses the progression of diabetic retinopathy. In this paper, we reveal a therapeutic effect of a selective PPARα modulator (SPPARMα), pemafibrate, against pathological angiogenesis in murine models of retinopathy. Oxygen-induced retinopathy (OIR) was induced in C57BL/6J mice by exposure to 85% oxygen from postnatal day eight (P8) for 72 h. Vehicle, pemafibrate or fenofibrate was administrated by oral gavage from P12 to P16 daily. Administration of pemafibrate, but not fenofibrate, significantly reduced pathological angiogenesis in OIR. After oral pemafibrate administration, expression levels of downstream PPARα targets such as acyl-CoA oxidase 1 (Acox1), fatty acid binding protein 4 (Fabp4), and fibroblast growth factor 21 (Fgf21) were significantly increased in the liver but not in the retina. A significant increase in plasma FGF21 and reduced retinal hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (Vegfa) were also observed after this treatment. In an in vitro HIF-luciferase assay, a long-acting FGF21 analogue, but not pemafibrate, suppressed HIF activity. These data indicate that SPPARMα pemafibrate administration may prevent retinal pathological neovascularization by upregulating FGF21 in the liver.

scholarly journals Human Endometrial Stromal Cell Differentiation is Stimulated by PPARβ/δ Activation: New Targets for Infertility?

2020 ◽  
Vol 105 (9) ◽  
pp. 2983-2995 ◽  
Author(s):  
Jie Yu ◽  
Sarah L Berga ◽  
Wei Zou ◽  
Augustine Rajakumar ◽  
Mingfei Man ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Growth Factor ◽  
Connexin 43 ◽  
Time Course ◽  
Estrogen Receptor Α ◽  
Peroxisome Proliferator ◽  
Endometrial Stromal Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Therapeutic Benefits

Abstract Context Implantation is a reproductive bottleneck in women, regulated by fluctuations in ovarian steroid hormone concentrations. However, other nuclear receptor ligands are modifiers of endometrial differentiation leading to successful pregnancy. In the present study we analyzed the effects of peroxisome-proliferator-activated receptor β/δ (PPARβ/δ) activation on established cellular biomarkers of human endometrial differentiation (decidualization). Objective The objective of this work is to test the effects of PPARβ/δ ligation on human endometrial cell differentiation. Design Isolated primary human endometrial stromal cells (ESCs) were treated with synthetic (GW0742) or natural (all trans-retinoic acid, RA) ligands of PPARβ/δ, and also with receptor antagonists (GSK0660, PT-S58, and ST247) in the absence or presence of decidualizing hormones (10 nM estradiol, 100 nM progesterone, and 0.5 mM dibutyryl cAMP [3′,5′-cyclic adenosine 5′-monophosphate]). In some cases interleukin (IL)-1β was used as an inflammatory stimulus. Time course and dose-response relationships were evaluated to determine effects on panels of well characterized in vitro biomarkers of decidualization. Results PPARβ/δ, along with estrogen receptor α (ERα) and PR-A and PR-B, were expressed in human endometrial tissue and isolated ESCs. GW0742 treatment enhanced hormone-mediated ESC decidualization in vitro as manifested by upregulation of prolactin, insulin-like growth factor-binding protein 1, IL-11, and vascular endothelial growth factor (VEGF) secretion and also increased expression of ERα, PR-A and PR-B, and connexin 43 (Cx43). RA treatment also increased VEGF, ERα, PR-A, and PR-B and an active, nonphosphorylated isoform of Cx43. IL-1β and PPARβ/δ antagonists inhibited biomarkers of endometrial differentiation. Conclusion Ligands that activate PPARβ/δ augment the in vitro expression of biomarkers of ESC decidualization. By contrast, PPARβ/δ antagonists impaired decidualization markers. Drugs activating these receptors may have therapeutic benefits for embryonic implantation.

scholarly journals Cocktail supplement with rosiglitazone: a novel inducer for chicken preadipocyte differentiation in vitro

2016 ◽  
Vol 36 (6) ◽  
Author(s):  
Bohan Cheng ◽  
Mengqi Wu ◽  
Songsong Xu ◽  
Xinyang Zhang ◽  
Yuxiang Wang ◽  
...  
Keyword(s):  
Fatty Acid Binding Protein ◽  
Peroxisome Proliferator ◽  
Induction Method ◽  
Preadipocyte Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Gpdh Activity ◽  
Acid Binding Protein ◽  
Glycerol 3 Phosphate Dehydrogenase

Chicken preadipocytes cultured in cocktail supplement with rosiglitazone resulted in a marked increase in lipid droplet accumulation, glycerol-3-phosphate dehydrogenase (GPDH) activity and mRNA expression of adipocyte fatty acid-binding protein (aP2), G0/G1 switch gene 2 (G0S2), peroxisome proliferator-activated receptor γ (PPARγ) and lipolysis. The present study provides a novel induction method for in vitro chicken preadipocyte differentiation.

scholarly journals miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1β

2016 ◽  
Vol 16 (4) ◽  
pp. 497-511 ◽  
Author(s):  
Hong Wang ◽  
Xi Yan ◽  
Li-Ya Ji ◽  
Xi-Tuan Ji ◽  
Ping Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Epigenetic Modification ◽  
Negative Control ◽  
Peroxisome Proliferator ◽  
Insulin Like Growth Factor ◽  
Peroxisome Proliferator Activated Receptor

Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor γ coactivator 1β as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor γ coactivator 1β-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.

scholarly journals PPARα Agonist Oral Therapy in Diabetic Retinopathy

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 433
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Kazuo Tsubota ◽  
Toshihide Kurihara
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Animal Studies ◽  
Early Stage ◽  
Vitreoretinal Surgery ◽  
Global Scale ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

Diabetic retinopathy (DR) is an eye condition that develops after chronically poorly-managed diabetes, and is presently the main cause for blindness on a global scale. Current treatments for DR such as laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery are only applicable at the late stages of DR and there are possibilities of significant adverse effects. Moreover, the forms of treatment available for DR are highly invasive to the eyes. Safer and more effective pharmacological treatments are required for DR treatment, in particular at an early stage. In this review, we cover recently investigated promising oral pharmacotherapies, the methods of which are safer, easier to use, patient-friendly and pain-free, in clinical studies. We especially focus on peroxisome proliferator-activator receptor alpha (PPARα) agonists in which experimental evidence suggests PPARα activation may be closely related to the attenuation of vascular damages, including lipid-induced toxicity, inflammation, an excess of free radical generation, endothelial dysfunction and angiogenesis. Furthermore, oral administration of selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) agonists may induce hepatic fibroblast growth factor 21 expression, indirectly resulting in retinal protection in animal studies. Our review will enable more comprehensive approaches for understanding protective roles of PPARα for the prevention of DR development.

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