Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney

1999 ◽  
Vol 277 (6) ◽  
pp. F966-F973 ◽  
Author(s):  
Tianxin Yang ◽  
Daniel E. Michele ◽  
John Park ◽  
Ann M. Smart ◽  
Zhiwu Lin ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Retinoid X Receptors ◽  
Nephron Segments ◽  
Process Formation ◽  
Nephron Segment ◽  
Altered Cell ◽  
X Receptors ◽  
Almost All

The discovery that 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) is a ligand for the γ-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPARα mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPARγ was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPARβ, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXRα was localized to PCT and IMCD, whereas RXRβ was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ2 significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPARα being involved in energy metabolism through regulating ACS in PCT and with PPARγ being involved in modulating RMIC growth and differentiation.

scholarly journals Peroxisome proliferator-activated receptor-γ agonists repress epithelial sodium channel expression in the kidney

2012 ◽  
Vol 302 (5) ◽  
pp. F540-F551 ◽  
Author(s):  
Emily Borsting ◽  
Vicki Pei-Chun Cheng ◽  
Chris K. Glass ◽  
Volker Vallon ◽  
Robyn Cunard
Keyword(s):  
Protein Expression ◽  
Sodium Channel ◽  
Mrna Expression ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Duct Cell ◽  
Kidney Cortex ◽  
Peroxisome Proliferator ◽  
Cortical Collecting Duct ◽  
Peroxisome Proliferator Activated Receptor

Thiazolidinediones (TZDs), known as peroxisome proliferator-activated receptor (PPAR) agonists, are used to treat type 2 diabetes. However, ∼5% of patients experience the treatment-limiting side effect of edema. Studies have implicated activation of the epithelial sodium channel (ENaC) as a cause of TZD-induced fluid retention, although there have been conflicting reports. The goal of this study was to resolve the role of PPARγ in control of ENaC isoforms in the kidney. Herein, we demonstrate in mice that rosiglitazone (RGZ), a PPARγ ligand, increases body weight and abdominal fat pad fluid content and reduces hematocrit. Seven days of RGZ decreases ENaCα and ENaCβ mRNA and ENaCγ protein expression in the kidney cortex, and acute treatment for 5 h with pioglitazone, another potent TZD, does not increase renal ENaC isoform mRNA or protein expression. Pioglitazone also decreases ENaCα and ENaCγ mRNA expression in a cortical collecting duct cell line. As no direct transcriptional studies had been conducted, we examined the PPARγ-dependent regulation of ENaC. Pioglitazone represses ENaCγ promoter activity, and this repression is partially relieved by inhibition of protein synthesis. Chromatin immunoprecipitation assays revealed that repression is associated with a decrease in histone H4K5 acetylation at the proximal ENaCγ promoter. In summary, TZDs do not increase ENaC mRNA expression in the kidney, and in fact repress the ENaCγ promoter via an indirect transcriptional mechanism.

scholarly journals Systemic PPARγ deletion causes severe disturbance in fluid homeostasis in mice

2015 ◽  
Vol 47 (11) ◽  
pp. 541-547 ◽  
Author(s):  
Li Zhou ◽  
Alexandra Panasiuk ◽  
Maicy Downton ◽  
Daqiang Zhao ◽  
Baoxue Yang ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight Gain ◽  
Collecting Duct ◽  
Urine Volume ◽  
Physiological Role ◽  
Urine Osmolality ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fluid Homeostasis

The pharmacological action of peroxisome proliferator-activated receptor (PPAR)γ in promoting sodium and water retention is well documented as highlighted by the major side-effect of body weight gain and edema associated with thiazolidinedione use. However, a possible physiological role of PPARγ in regulation of fluid metabolism has not been reported by previous studies. Here we analyzed fluid metabolism in inducible whole-body PPARγ knockout mice. The null mice developed severe polydipsia and polyuria, reduced urine osmolality, and modest hyperphagia. The phenomenon persisted during 3 days of pair feeding and pair drinking, accompanied by progressive weight loss. After 24 h water deprivation, the null mice had a lower urine osmolality, a higher urine volume, a greater weight loss, and a greater rise in hematocrit than the floxed control. Urinary vasopressin (AVP) excretion was not different between the genotypes under basal condition or after WD. The response of urine osmolality to acute and chronic 1-desamino-8-d-arginine vasopressin treatment was attenuated in the null mice, but the total abundance or phosphorylation of aquaporin 2 (AQP2) in the kidney or AVP-induced cAMP production in inner medullary collecting duct suspensions was unaffected. Overall, PPARγ participates in physiological control of fluid homeostasis through an unknown mechanism involving cAMP/AQP2-independent enhancement of AVP response.

scholarly journals Effect of LXR/RXR agonism on brain and CSF Aβ40 levels in rats

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 138 ◽  
Author(s):  
Songli Wang ◽  
Paul Wen ◽  
Stephen Wood
Keyword(s):  
Principal Component ◽  
Amyloid Plaques ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Peroxisome Proliferator Activated Receptor ◽  
Abnormal Accumulation ◽  
Csf Levels ◽  
X Receptors ◽  
The Brain ◽  
Receptor Family

Alzheimer's disease (AD) is characterized pathologically by the presence of amyloid plaques and neurofibrillary tangles.  The amyloid hypothesis contends that the abnormal accumulation of Aβ, the principal component of amyloid plaques, plays an essential role in initiating the disease.  Impaired clearance of soluble Aβ from the brain, a process facilitated by apolipoprotein E (APOE), is believed to be a contributing factor in plaque formation.  APOE expression is transcriptionally regulated through the action of a family of nuclear receptors including the peroxisome proliferator-activated receptor gamma and liver X receptors (LXRs) in coordination with retinoid X receptors (RXRs).  It has been previously reported that various agonists of this receptor family can influence brain Aβ levels in rodents.  In this study we investigated the effects of LXR/RXR agonism on brain and cerebrospinal fluid (CSF) levels of Aβ40 in naïve rats.  Treatment of rats for 3 days or 7 days with the LXR agonist, TO901317 or the RXR agonist, Bexarotene did not result in significant changes in brain or CSF Aβ40 levels.

scholarly journals Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression

2004 ◽  
Vol 24 (8) ◽  
pp. 3430-3444 ◽  
Author(s):  
Jong Bae Seo ◽  
Hyang Mi Moon ◽  
Woo Sik Kim ◽  
Yun Sok Lee ◽  
Hyun Woo Jeong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Adipocyte Differentiation ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Gene Promoters ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Gene Expression ◽  
X Receptors

ABSTRACT Liver X receptors (LXRs) are nuclear hormone receptors that regulate cholesterol and fatty acid metabolism in liver tissue and in macrophages. Although LXR activation enhances lipogenesis, it is not well understood whether LXRs are involved in adipocyte differentiation. Here, we show that LXR activation stimulated the execution of adipogenesis, as determined by lipid droplet accumulation and adipocyte-specific gene expression in vivo and in vitro. In adipocytes, LXR activation with T0901317 primarily enhanced the expression of lipogenic genes such as the ADD1/SREBP1c and FAS genes and substantially increased the expression of the adipocyte-specific genes encoding PPARγ (peroxisome proliferator-activated receptor γ) and aP2. Administration of the LXR agonist T0901317 to lean mice promoted the expression of most lipogenic and adipogenic genes in fat and liver tissues. It is of interest that the PPARγ gene is a novel target gene of LXR, since the PPARγ promoter contains the conserved binding site of LXR and was transactivated by the expression of LXRα. Moreover, activated LXRα exhibited an increase of DNA binding to its target gene promoters, such as ADD1/SREBP1c and PPARγ, which appeared to be closely associated with hyperacetylation of histone H3 in the promoter regions of those genes. Furthermore, the suppression of LXRα by small interfering RNA attenuated adipocyte differentiation. Taken together, these results suggest that LXR plays a role in the execution of adipocyte differentiation by regulation of lipogenesis and adipocyte-specific gene expression.

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