Critical roles of the nuclear receptor PPARβ (peroxisome-proliferator-activated receptor β) in skin wound healing

Tan, Nguan Soon; Michalik, Liliane; Di‐Poï, Nicolas; Desvergne, Béatrice; Wahli, Walter

doi:10.1042/bst0320097

Cited by 41 publications

(27 citation statements)

References 37 publications

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“…39), and as a critical intermediate in skin wound healing (reviewed in Ref. 47). Research on the metabolic role of PPAR␤/␦ has focused on regulation of fatty acid oxidation in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver

Sanderson

Boekschoten

Desvergne

et al. 2010

Physiological Genomics

123

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Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) β/δ in liver. Here we set out to better elucidate the function of PPARβ/δ in liver by comparing the effect of PPARα and PPARβ/δ deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARα and PPARβ/δ deletion was similar, whereas in fasted state the effect of PPARα deletion was much more pronounced, consistent with the pattern of gene expression of PPARα and PPARβ/δ. Minor overlap was found between PPARα- and PPARβ/δ-dependent gene regulation in liver. Pathways upregulated by PPARβ/δ deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARβ/δ deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARβ/δ−/− mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARβ/δ target genes. In contrast to PPARα−/− mice, no changes in plasma free fatty acid, plasma β-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARβ/δ−/− mice. Our data indicate that PPARβ/δ governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver.

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Section: Discussionmentioning

confidence: 99%

Transcriptional profiling reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver

Sanderson

Boekschoten

Desvergne

et al. 2010

Physiological Genomics

123

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“…Newly developed synthetic ligands and genetically modified mouse models for PPAR-δ have rapidly advanced our understanding of the important roles of PPAR-δ in tissue development and repair and angiogenesis (Piqueras et al, 2007) and inflammation and metabolism (Leibowitz et al, 2000;Dressel et al, 2003;Tan et al, 2001Tan et al, , 2004. Our results show that the rare C-allele is present in the healthy Tunisian population at a frequency similar to that in Caucasian men (0.189 vs 0.18, respectively) (Skogsberg et al, PPAR-delta polymorphism and CAD 2003a).…”

Section: Discussionmentioning

confidence: 99%

+294T/C polymorphism in the PPAR-δ gene is associated with risk of coronary artery disease in normolipidemic Tunisians

Jguirim-Souissi

Jelassi²,

Hrira³

et al. 2010

Genet. Mol. Res.

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“…Interestingly, the expression of PPARα is upregulated by antiinflammatory glucocorticoids, which increase during injury (4, 5). The inhibitory effect of PPARα on NF-κB action may create a negative feedback loop, which would explain the transient PPARα expression that allows control of early inflammation (5).…”

Section: Ppar Involvement In Healing Stratified Epithelia: Skin Woundmentioning

confidence: 99%

Involvement of PPAR nuclear receptors in tissue injury and wound repair

Michalik

Wahli²

2006

Journal of Clinical Investigation

Self Cite

198

134

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Tissue damage resulting from chemical, mechanical, and biological injury, or from interrupted blood flow and reperfusion, is often life threatening. The subsequent tissue response involves an intricate series of events including inflammation, oxidative stress, immune cell recruitment, and cell survival, proliferation, migration, and differentiation. In addition, fibrotic repair characterized by myofibroblast transdifferentiation and the deposition of ECM proteins is activated. Failure to initiate, maintain, or stop this repair program has dramatic consequences, such as cell death and associated tissue necrosis or carcinogenesis. In this sense, inflammation and oxidative stress, which are beneficial defense processes, can become harmful if they do not resolve in time. This repair program is largely based on rapid and specific changes in gene expression controlled by transcription factors that sense injury. PPARs are such factors and are activated by lipid mediators produced after wounding. Here we highlight advances in our understanding of PPAR action during tissue repair and discuss the potential for these nuclear receptors as therapeutic targets for tissue injury. An overview of tissue injuryThe clinical significance of tissue injury and the need for therapeutic agents to treat organ damage have called for an improved understanding of the causes of tissue injury and subsequent healing. The complex nature of these processes creates a challenge in identifying the specific cell types and biochemical pathways involved. Moreover, tissue protection and regeneration require tight control of cell survival and death, cell growth and differentiation, and ECM remodeling and breakdown. Chemical, biological, and mechanical stress is deleterious to epithelial tissue, and even whole organs are vulnerable to damage. For example, the liver, which metabolizes nutrients and drugs absorbed from the digestive tract, is particularly susceptible to injury, since all blood leaving the intestines and stomach must pass through it before reaching the rest of the body. Organ damage also occurs in response to an inadequate supply of oxygen (hypoxia), usually caused by blood vessel constriction or obstruction (ischemia). Under normal physiological conditions, oxygenation levels and sensitivity to hypoxia differ among the various organs. Since short periods of ischemia and reperfusion (ischemia/reperfusion, or I/R) cause extensive damage, the goal of the survival response is to maintain tissue viability. As a result, the hypoxia response requires optimal revascularization for efficient recovery.Inflammation is a major component of early healing, and its control is essential for efficient repair. The inflammatory cytokines and eicosanoids produced during the first hours after injury recruit neutrophils and macrophages to the wound. These cells amplify the early response through their production of additional inflammatory mediators. Some of these factors promote cell proliferation and migration and are thus directly involved in wound closure. ...

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Critical roles of the nuclear receptor PPARβ (peroxisome-proliferator-activated receptor β) in skin wound healing

Cited by 41 publications

References 37 publications

Transcriptional profiling reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver

Transcriptional profiling reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver

+294T/C polymorphism in the PPAR-δ gene is associated with risk of coronary artery disease in normolipidemic Tunisians

Involvement of PPAR nuclear receptors in tissue injury and wound repair

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