scholarly journals Investigating the Role of PPARβ/δ in Retinal Vascular Remodeling Using Pparβ/δ-Deficient Mice

2020 ◽  
Vol 21 (12) ◽  
pp. 4403 ◽  
Author(s):  
Sze Yuan Ho ◽  
Yuet Ping Kwan ◽  
Beiying Qiu ◽  
Alison Tan ◽  
Hannah Louise Murray ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Vessel Remodeling ◽  
Deficient Mice

Peroxisome proliferator-activated receptor (PPAR)β/δ is a member of the nuclear receptor superfamily of transcription factors, which plays fundamental roles in cell proliferation and differentiation, inflammation, adipogenesis, and energy homeostasis. Previous studies demonstrated a reduced choroidal neovascularization (CNV) in Pparβ/δ-deficient mice. However, PPARβ/δ’s role in physiological blood vessel formation and vessel remodeling in the retina has yet to be established. Our study showed that PPARβ/δ is specifically required for disordered blood vessel formation in the retina. We further demonstrated an increased arteriovenous crossover and wider venous caliber in Pparβ/δ-haplodeficient mice. In summary, these results indicated a critical role of PPARβ/δ in pathological angiogenesis and blood vessel remodeling in the retina.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

scholarly journals IL-15 Is Required for Postexercise Induction of the Pro-Oxidative Mediators PPARδ and SIRT1 in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 143-155 ◽  
Author(s):  
LeBris S. Quinn ◽  
Barbara G. Anderson ◽  
Jennifer D. Conner ◽  
Tami Wolden-Hanson ◽  
Taylor J. Marcell
Keyword(s):  
Physical Exercise ◽  
Gastrocnemius Muscle ◽  
Sirtuin 1 ◽  
Treadmill Running ◽  
Separate Experiment ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Deficient Mice

Physical exercise induces transient upregulation of the pro-oxidative mediators peroxisome proliferator-activated receptor-δ (PPARδ), silent information regulator of transcription (sirtuin)-1 (SIRT1), PPARγ coactivator 1α (PGC-1α), and PGC-1β in skeletal muscle. To determine the role of the cytokine IL-15 in acute postexercise induction of these molecules, expression of these factors after a bout of exhaustive treadmill running was examined in the gastrocnemius muscle of untrained control and IL-15–knockout (KO) mice. Circulating IL-15 levels increased transiently in control mice after exercise. Control mice, but not IL-15–KO mice, upregulated muscle PPARδ and SIRT1 protein after exercise, accompanied by a complex pattern of mRNA expression for these factors. However, in exhaustive exercise, control mice ran significantly longer than IL-15–KO mice. Therefore, in a second experiment, mice were limited to a 20-minute run, after which a similar pattern of induction of muscle PPARδ and SIRT1 protein by control mice only was observed. In a separate experiment, IL-15–KO mice injected systemically with recombinant IL-15 upregulated muscle PPARδ and SIRT1 mRNA within 30 minutes and also exhibited increased muscle PPARδ protein levels by 3 hours. After exercise, both control and IL-15–KO mice downregulated IL-15 receptor-α (IL-15Rα) mRNA, whereas IL-15Rα–deficient mice exhibited constitutively elevated circulating IL-15 levels. These observations indicate IL-15 release after exercise is necessary for induction of PPARδ and SIRT1 at the protein level in muscle tissue and suggest that exercise releases IL-15 normally sequestered by the IL-15Rα in the resting state. These findings could be used to develop an IL-15–based strategy to induce many of the metabolic benefits of physical exercise.

scholarly journals Peroxisome Proliferator-Activated Receptor γ and PGC-1α in Cancer: Dual Actions as Tumor Promoter and Suppressor

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Seong-Hoon Yun ◽  
Sang-Heum Han ◽  
Joo-In Park
Keyword(s):  
Metabolic Pathways ◽  
Energy Homeostasis ◽  
Tumor Promoter ◽  
Clinical Implications ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Action Mechanisms ◽  
Important Regulator

Peroxisome proliferator-activated receptor γ (PPARγ) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPARγ coactivator-1α (PGC-1α), initially identified as a PPARγ-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism and energy homeostasis. The role of PGC-1α in diabetes, neurodegeneration, and cardiovascular disease is particularly well known. PGC-1α is also now known to play important roles in cancer, independent of the role of PPARγ in cancer. Though many researchers have studied the expression and clinical implications of PPARγ and PGC-1α in cancer, there are still many controversies about the role of PPARγ and PGC-1α in cancer. This review examines and summarizes some recent data on the role and action mechanisms of PPARγ and PGC-1α in cancer, respectively, particularly the recent progress in understanding the role of PPARγ in several cancers since our review was published in 2012.

scholarly journals Contribution of cell death signaling to blood vessel formation

2021 ◽  
Vol 78 (7) ◽  
pp. 3247-3264
Author(s):  
Nathalie Tisch ◽  
Carmen Ruiz de Almodóvar
Keyword(s):  
Cell Death ◽  
Blood Vessel ◽  
Vascular System ◽  
Current Knowledge ◽  
Surrounding Tissue ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Vessel Remodeling ◽  
Vessel Regression ◽  
Cell Death Signaling

AbstractThe formation of new blood vessels is driven by proliferation of endothelial cells (ECs), elongation of maturing vessel sprouts and ultimately vessel remodeling to create a hierarchically structured vascular system. Vessel regression is an essential process to remove redundant vessel branches in order to adapt the final vessel density to the demands of the surrounding tissue. How exactly vessel regression occurs and whether and to which extent cell death contributes to this process has been in the focus of several studies within the last decade. On top, recent findings challenge our simplistic view of the cell death signaling machinery as a sole executer of cellular demise, as emerging evidences suggest that some of the classic cell death regulators even promote blood vessel formation. This review summarizes our current knowledge on the role of the cell death signaling machinery with a focus on the apoptosis and necroptosis signaling pathways during blood vessel formation in development and pathology.

scholarly journals Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation

2018 ◽  
Vol 22 (11) ◽  
pp. 5244-5256 ◽  
Author(s):  
Sandra Atienzar-Aroca ◽  
Gemma Serrano-Heras ◽  
Aida Freire Valls ◽  
Carmen Ruiz de Almodovar ◽  
Maria Muriach ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Blood Vessel ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Blood Vessel Formation ◽  
Vessel Formation

scholarly journals PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice

2020 ◽  
Vol 21 (6) ◽  
pp. 2061 ◽  
Author(s):  
Yaping Wang ◽  
Takero Nakajima ◽  
Frank J. Gonzalez ◽  
Naoki Tanaka
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Cancer ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Regulators

Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver.

Role of EGFL7 during blood vessel formation and remodelling

2006 ◽  
Vol 45 (3) ◽  
pp. e126-e127
Author(s):  
Maike Schmidt ◽  
Tanya Smyczek ◽  
Weilan Ye
Keyword(s):  
Blood Vessel ◽  
Blood Vessel Formation ◽  
Vessel Formation

scholarly journals A Role for PPARβ/δin Tumor Stroma and Tumorigenesis

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Rolf Müller ◽  
Martin Kömhoff ◽  
Jeffrey M. Peters ◽  
Sabine Müller-Brüsselbach
Keyword(s):  
Fatty Acid ◽  
Cellular Differentiation ◽  
Tumor Stroma ◽  
Endothelial Cell Proliferation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endogenous Fatty Acid ◽  
Blood Vessel Formation ◽  
Fatty Acid Catabolism

Peroxisome proliferator-activated receptor-β/δ(PPARβ/δ) is a transcription factor that is activated by endogenous fatty acid ligands and by synthetic agonists. Its role in the regulation of skeletal muscle fatty acid catabolism, glucose homeostasis, and cellular differentiation has been established in multiple studies. On the contrary, a role for PPARβ/δin tumorigenesis is less clear because there are contradictory reports in the literature. However, the majority of these studies have not examined the role of PPARβ/δin the tumor stroma. Recent evidence suggests that stromal PPARβ/δregulates tumor endothelial cell proliferation and promotes differentiation leading to the properly orchestrated events required for tumor blood vessel formation. This review briefly summarizes the significance of these studies that may provide clues to help explain the reported discrepancies in the literature regarding the role of PPARβ/δin tumorigenesis.

scholarly journals Glypican-3 Enhances Reprogramming of Glucose Metabolism in Liver Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Gebing Yao ◽  
Jikai Yin ◽  
Qing Wang ◽  
Rui Dong ◽  
Jianguo Lu
Keyword(s):  
Glucose Metabolism ◽  
Liver Cancer ◽  
Mitochondrial Biogenesis ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Strong Line ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The One

Glypican-3(GPC3) is a transmembrane protein which has been found to be frequently overexpressed on the surfaces of liver cancer (LC) cells, which contributes to both the growth and metastasis of LC cells. Recently, the expression of GPC3 has been reported to be inversely associated with glucose metabolism activity in LC patients, suggesting that GPC3 may play a role in the regulation of glucose metabolism in LC. However, the role of GPC3 in glucose metabolism reprogramming, as well as in LC cell growth and metastasis, is unknown. Here, we found that GPC3 significantly contributed to the reprogramming of glucose metabolism in LC cells. On the one hand, GPC3 enhanced the glycolysis of LC cells through upregulation of the glycolytic genes of Glut1, HK2, and LDH-A. On the other hand, GPC3 repressed mitochondrial respiration through downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), which has been well known as a crucial regulator in mitochondrial biogenesis. Mechanistic investigations revealed that HIF-1α was involved in both GPC3-regulated upregulation of glycolytic genes of HK2, PKM2, and Glut1 and downregulation of mitochondrial biogenesis regulator PGC-1α in LC cells. Additionally, GPC3-regulated reprogramming of glucose metabolism played a critical role in the growth and metastasis of LC cells. Conclusion. Our findings demonstrate that GPC3 is a critical regulator of glucose metabolism reprogramming in LC cells, which provides a strong line of evidence for GPC3 as an important therapeutic target to normalize glucose metabolic aberrations responsible for LC progression.

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