15-Deoxy-∆-^12,14-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-γ: Function and Mechanism

Abstract

15-Deoxy-∆-12,14-prostaglandin J2 (15d-PGJ2), a natural peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has been explored in some detail over the last 20 years. By triggering the PPAR-γ signalling pathway, it plays many roles and exerts antitumour, anti-inflammatory, antioxidation, antifibrosis, and antiangiogenesis effects. Although many synthetic PPAR-γ receptor agonists have been developed, as an endogenous product of PPAR-γ receptors, 15d-PGJ2 has beneficial characteristics including rapid expression and the ability to contribute to a natural defence mechanism. In this review, we discuss the latest advances in our knowledge of the biological role of 15d-PGJ2 mediated through PPAR-γ. It is important to understand its structure, synthesis, and functional mechanisms to develop preventive agents and limit the progression of associated diseases.

Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis

“…PPAR-γ plays an important role in maintaining energy homeostasis through the modulation of glucose and lipid metabolism, and PPAR-γ is usually overexpressed in cancer cells causing accelerated tumor growth [58,59]. However, the role of PPAR-γ agonists and antagonists in tumor treatment is complex, as both have been found to inhibit the growth of tumor cells [58,[60][61][62]. PPAR-γ has been found to promote glucose uptake during lipid metabolism, and can induce the expression of glycolytic proteins, including GLUT-4 [63].…”

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

“…In a previous study, our team demonstrated that 15-Deoxy-△-12,14-Prostaglandin J2 (15d-PGJ2) can improve liver function by activating PPAR-γ to inhibit NF-κB p65, and the role and mechanism of the PPAR-γ natural ligand activator-15d-PGJ2 in liver has since reviewed. [41][42][43] Herein, we carried out molecular biological studies on PPAR-γ as well as upstream and downstream pathways. Firstly, we found that activation and expression of PPAR-γ in IR were significantly inhibited, whereas PPAR-γ was activated in drug treatment groups, corresponding to improved liver function.…”

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

“…In interacting with agonists, PPARs translocate to the nucleus and make a heterodimer with retinoid X receptor α (RXRα) [43]. As a result, genes encoding insulin-1 and insulin-2 receptors (IRS-1 and IRS-2), as well as TNF-α, NF-κB, and activator protein-1 (AP-1), are expressed [44]. PPARs inhibit many transcription factors possessing a proinflammatory action: NF-κB, AP-1, protein C/EBP (CCAAT/enhancer-binding protein), and signal transducers and activators of transcription (STAT).…”

“…15-Deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) is the first discovered endogenous PPARγ ligand that exerts its effect by developing a PPRE response [44]. Heterodimers with RXRα receptors are formed after binding 15d-PGJ2 and PPARγ together.…”