Expression of the Peroxisome Proliferator-Activated Receptor (PPAR) in the Mouse Colonic Mucosa

Mansén, Anethe; Guardiola-Diaz, Hebe M.; Rafter, Joseph; Branting, Christina; Gustafsson, Jan‐Åke

doi:10.1006/bbrc.1996.0832

Cited by 194 publications

(145 citation statements)

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“…In another recent study, quantification of PPAR mRNA by ribonuclease protection assay revealed relatively high expression of PPAR␥ and PPAR␤ in adult mouse colon compared to small intestine. In contrast, PPAR␣ expression was higher in the intestinal mucosa (Mansen et al 1996). Furthermore, PPAR␥ is reported to be also expressed in human Sarraf et al 1998) and rodent (Lefebvre et al 1998;Saez et al 1998) colon tumor cells.…”

Section: Expression Of Ppars In Human Digestive Tractmentioning

confidence: 90%

Differential Expression of Peroxisome Proliferator-activated Receptors (PPARs) in the Developing Human Fetal Digestive Tract

Huin¹,

Corriveau²,

Bianchi³

et al. 2000

J Histochem Cytochem.

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SUMMARY We investigated the spatiotemporal distributions of the different peroxisome proliferator-activated receptor (PPAR) isotypes (α, β, and α) during development (Week 7 to Week 22 of gestation) of the human fetal digestive tract by immunohistochemistry using specific polyclonal antibodies. The PPAR subtypes, including PPARα, are expressed as early as 7 weeks of development in cell types of endodermal and mesodermal origin. The presence of PPARα was also found by Western blotting and nuclease-S1 protection assay, confirming that this subtype is not adipocyte-specific. PPARα, PPARβ, and PPARα exhibit different patterns of expression during morphogenesis of the digestive tract. Whatever the stage and the gut region (except the stomach) examined, PPARα is expressed at a high level, suggesting some fundamental role for this receptor in development and/or physiology of the human digestive tract.

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Section: Expression Of Ppars In Human Digestive Tractmentioning

confidence: 90%

Differential Expression of Peroxisome Proliferator-activated Receptors (PPARs) in the Developing Human Fetal Digestive Tract

Huin¹,

Corriveau²,

Bianchi³

et al. 2000

J Histochem Cytochem.

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“…This is perhaps most evident in the colon, which was found to express levels of PPAR␥ mRNA nearly equivalent to that found in adipocytes (19). Within the colon, the highest levels of receptor expression have been observed in post-mitotic, differentiated epithelial cells (20,21). Consistent with this expression pattern, activation of PPAR␥ in cultured colon cancer cells induces growth inhibition and an increase in several markers of cellular differentiation (22,23).…”

mentioning

confidence: 83%

Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells

Gupta¹,

Brockman²,

Sarraf³

et al. 2001

Journal of Biological Chemistry

185

123

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Activation of the nuclear hormone peroxisome proliferator-activated receptor ␥ (PPAR␥) inhibits cell growth and promotes differentiation in a broad spectrum of epithelial derived tumor cell lines. Here we utilized microarray technology to identify PPAR␥ gene targets in intestinal epithelial cells. For each gene, the induction or repression was seen with two structurally distinct PPAR␥ agonists, and the change in expression could be blocked by co-treatment with a specific PPAR␥ antagonist. A majority of the genes could be regulated independently by a retinoid X receptor specific agonist. Genes implicated in lipid transport or storage (adipophilin and liver fatty acid-binding protein) were also activated by agonists of PPAR subtypes ␣ and/or ␦. -independent, carcinoembryonic antigendependent homotypic aggregation, suggesting a potential role for PPAR␥ in regulating intercellular adhesion. Collectively, these results will help define the mechanisms by which PPAR␥ regulates intestinal epithelial cell biology.

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“…Mouse PPA R-2 is derived by alternative splicing from the same gene as PPA R-1 and contains an additional 30 amino acids at the NH 2 -terminus (29,30). P PA R-2 expression is limited to adipose tissue (31), whereas PPA R-1 is expressed in adipose tissue, liver, muscle, macrophages, and colon (32)(33)(34). The relative contribution of the two isoforms to the antidiabetic activity of the TZDs is unknown.…”

Section: A B Cmentioning

confidence: 99%

Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone.

Camp¹,

Li²,

Wise³

et al. 2000

Diabetes

214

122

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The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-a c t i v a t e d receptor (PPA R )-and exert their antihyperglycemic e ffects by regulation of PPA R--responsive genes. We report here that PPA R-activation by troglitazone depends on the experimental setting. Troglitazone acts as a partial agonist for PPA R-in transfected muscle (C2C12) and kidney (HEK 293T) cells, producing a submaximal transcriptional response (1.8-to 2.5-fold activation) compared with rosiglitazone (7.4-to 13-fold activation). Additionally, troglitazone antagonizes rosiglitazone-stimulated PPA R-transcriptional activity. Limited protease digestion of PPA R-suggests conformational differences in the receptor bound to troglitazone versus rosiglitazone. Consistent with this fin d i n g , an in vitro coactivator association assay demonstrated that troglitazone-bound PPA R-recruited the transcriptional coactivators p300 and steroid receptor coactivator 1 less efficiently than rosiglitazone-bound receptor. In contrast to these observations, troglitazone behaves as a full agonist of PPA R-in 3T3L1 adipocytes. Tw odimensional protein gel electrophoresis demonstrated that troglitazone and rosiglitazone regulated distinct but overlapping sets of genes in several cell types. Thus, troglitazone may behave as a partial agonist under certain physiological circumstances and as a full agonist in others. These differences could be caused by variations in the amount of specific cofactors, differences in PPA R response elements, or the presence of different isoforms of PPA R-. D i a b e t e s 4 9 :5 3 9-547, 2000 T ype 2 diabetes is characterized by decreased insulin sensitivity of peripheral tissues. Glucose homeostasis is maintained under these circumstances by increased insulin secretion from pancreatic -cells. In some cases, the -cell is unable to maintain increased output. The antidiabetic thiazolidinediones (TZDs), such as troglitazone, improve peripheral insulin sensitivity, leading to reduced blood glucose and insulin levels and the preservation of pancreatic function (1-4). Improvement of insulin sensitivity by TZDs is most likely due to the activation of the peroxisome proliferator-activated receptor (PPA R )-(5). The TZDs are high-affinity ligands for PPA R-in vitro, and the rank order of receptor affinity correlates with their in vivo hypoglycemic activity (6), with one reported exception (7). Although many of the molecular details are not clearly understood, a model has emerged in which activated PPA R-m o dulates the transcriptional activity of a set of genes encoding proteins that are important in glucose and lipid metabolism. H o w e v e r, the identity of these genes and the precise pathways leading to the normalization of insulin sensitivity remain largely unknown.R e c e n t l y, the X-ray crystal structure of the ligand-binding domain of PPA R-has been elucidated (3,8), revealing that ligand binding causes a conformational change within P PA R-such...

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Expression of the Peroxisome Proliferator-Activated Receptor (PPAR) in the Mouse Colonic Mucosa

Cited by 194 publications

References 0 publications

Differential Expression of Peroxisome Proliferator-activated Receptors (PPARs) in the Developing Human Fetal Digestive Tract

Differential Expression of Peroxisome Proliferator-activated Receptors (PPARs) in the Developing Human Fetal Digestive Tract

Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells

Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone.

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