Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: gene profiling in pulmonary hypertension.

Abstract:

:Peroxisome proliferator-activated receptor type gamma (PPARgamma) is a subgroup of the PPAR transcription factor family. Recent studies indicate that loss of PPARgamma is associated with the development of pulmonary hypertension (PH). We hypothesized that the endothelial dysfunction associated with PPARgamma inhibition may play an important role in the disease process by altering cellular gene expression and signaling cascades. We utilized microarray analysis to determine if PPARgamma inhibition induced changes in gene expression in pulmonary arterial endothelial cells (PAEC). We identified 100 genes and expressed sequence tags (ESTs) that were upregulated by >1.5-fold and 21 genes and ESTs that were downregulated by >1.3-fold (P < 0.05) by PPARgamma inhibition. The upregulated genes can be broadly classified into four functional groups: cell cycle, angiogenesis, ubiquitin system, and zinc finger proteins. The genes with the highest fold change in expression: hyaluronan-mediated motility receptor (HMMR), VEGF receptor 2 (Flk-1), endothelial PAS domain protein 1 (EPAS1), basic fibroblast growth factor (FGF-2), and caveolin-1 in PAEC were validated by real time RT-PCR. We further validated the upregulation of HMMR, Flk-1, FGF2, and caveolin-1 by Western blot analysis. In keeping with the microarray results, PPARgamma inhibition led to re-entry of cell cycle at G(1)/S phase and cyclin C upregulation. PPARgamma inhibition also exacerbated VEGF-induced endothelial barrier disruption. Finally we confirmed the downregulation of PPARgamma and the upregulation of HMMR, Flk-1, FGF2, and Cav-1 proteins in the peripheral lung tissues of an ovine model of PH. In conclusion, we have identified an array of endothelial genes modulated by attenuated PPARgamma signaling that may play important roles in the development of PH.

journal_name

Physiol Genomics

journal_title

Physiological genomics

authors

Tian J,Smith A,Nechtman J,Podolsky R,Aggarwal S,Snead C,Kumar S,Elgaish M,Oishi P,Göerlach A,Fratz S,Hess J,Catravas JD,Verin AD,Fineman JR,She JX,Black SM

doi

10.1152/physiolgenomics.00094.2009

subject

Has Abstract

pub_date

2009-12-30 00:00:00

pages

48-60

issue

1

eissn

1094-8341

issn

1531-2267

pii

00094.2009

journal_volume

40

pub_type

杂志文章
  • Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling.

    abstract::Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor anal...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00027.2015

    authors: Richards EM,Rabaglino MB,Antolic A,Wood CE,Keller-Wood M

    更新日期:2015-09-01 00:00:00

  • Ultrafine mapping of Dyscalc1 to an 80-kb chromosomal segment on chromosome 7 in mice susceptible for dystrophic calcification.

    abstract::In mice, dystrophic cardiovascular calcification (DCC) is controlled by a major locus on proximal mouse chromosome 7 named Dyscalc1. Here we present a strategy that combines in silico analysis, expression analysis, and extensive sequencing for ultrafine mapping of the Dyscalc1 locus. We subjected 15 laboratory mouse s...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00133.2006

    authors: Aherrahrou Z,Doehring LC,Kaczmarek PM,Liptau H,Ehlers EM,Pomarino A,Wrobel S,Götz A,Mayer B,Erdmann J,Schunkert H

    更新日期:2007-01-17 00:00:00

  • Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation.

    abstract::Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human sk...

    journal_title:Physiological genomics

    pub_type: 杂志文章,随机对照试验

    doi:10.1152/physiolgenomics.00157.2007

    authors: Safdar A,Yardley NJ,Snow R,Melov S,Tarnopolsky MA

    更新日期:2008-01-17 00:00:00

  • Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults.

    abstract::We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the freq...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00048.2002

    authors: Dengel DR,Brown MD,Ferrell RE,Reynolds TH 4th,Supiano MA

    更新日期:2002-10-29 00:00:00

  • Genomic profiling of developing cardiomyocytes from recombinant murine embryonic stem cells reveals regulation of transcription factor clusters.

    abstract::Cardiomyocytes derived from pluripotent embryonic stem cells (ESC) have the advantage of providing a source for standardized cell cultures. However, little is known on the regulation of the genome during differentiation of ESC to cardiomyocytes. Here, we characterize the transcriptome of the mouse ESC line CM7/1 durin...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.90287.2008

    authors: Seewald MJ,Ellinghaus P,Kassner A,Stork I,Barg M,Niebrügge S,Golz S,Summer H,Zweigerdt R,Schräder EM,Feicht S,Jaquet K,Reis S,Körfer R,Milting H

    更新日期:2009-06-10 00:00:00

  • Long human CHGA flanking chromosome 14 sequence required for optimal BAC transgenic "rescue" of disease phenotypes in the mouse Chga knockout.

    abstract::Chromogranin A (CHGA) plays a catalytic role in formation of catecholamine storage vesicles and also serves as precursor to the peptide fragment catestatin, a catecholamine secretory inhibitor whose expression is diminished in the hypertensive individuals. We previously reported the hypertensive, hyperadrenergic pheno...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00086.2009

    authors: Vaingankar SM,Li Y,Corti A,Biswas N,Gayen J,O'Connor DT,Mahata SK

    更新日期:2010-03-03 00:00:00

  • HIF signaling and overall gene expression changes during hypoxia and prolonged exercise differ considerably.

    abstract::Exercise as well as hypoxia cause an increase in angiogenesis, changes in mitochondrial density and alterations in metabolism, but it is still under debate whether the hypoxia inducible factor (HIF) is active during both situations. In this study gene expression analysis of zebrafish larvae that were raised under norm...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00250.2010

    authors: Kopp R,Köblitz L,Egg M,Pelster B

    更新日期:2011-05-13 00:00:00

  • Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease.

    abstract::Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00204.2006

    authors: Glyn-Jones S,Song S,Black MA,Phillips AR,Choong SY,Cooper GJ

    更新日期:2007-02-12 00:00:00

  • Genomic analysis distinguishes phases of early development of the mouse atrio-ventricular canal.

    abstract::Valve formation during embryonic heart development involves a complex interplay of regional specification, cell transformations, and remodeling events. While many studies have addressed the role of specific genes during this process, a global understanding of the genetic basis for the regional specification and develo...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00142.2009

    authors: Vrljicak P,Chang AC,Morozova O,Wederell ED,Niessen K,Marra MA,Karsan A,Hoodless PA

    更新日期:2010-02-04 00:00:00

  • Evolutionary changes in heat-inducible gene expression in lines of Escherichia coli adapted to high temperature.

    abstract::The involvement of heat-inducible genes, including the heat-shock genes, in the acute response to temperature stress is well established. However, their importance in genetic adaptation to long-term temperature stress is less clear. Here we use high-density arrays to examine changes in expression for 35 heat-inducible...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00034.2002

    authors: Riehle MM,Bennett AF,Lenski RE,Long AD

    更新日期:2003-06-24 00:00:00

  • Steroid sulfatase gene variation and DHEA responsiveness to resistance exercise in MERET.

    abstract::Genetic influences and endurance exercise have been shown to alter circulating concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate, DHEAS. We hypothesized that acute resistance exercise (RE) and training (RET) would increase DHEA steroids, and the magnitude of the increase would be influenced by...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00097.2003

    authors: Riechman SE,Fabian TJ,Kroboth PD,Ferrell RE

    更新日期:2004-05-19 00:00:00

  • Knockin mice with Leu9'Ser alpha4-nicotinic receptors: substantia nigra dopaminergic neurons are hypersensitive to agonist and lost postnatally.

    abstract::This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knockin mouse strain bearing hypersensitive nicotinic alpha4-receptor subunits ("L9'S mice"). Adult brains of L9'S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic i...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00012.2004

    authors: Orb S,Wieacker J,Labarca C,Fonck C,Lester HA,Schwarz J

    更新日期:2004-08-11 00:00:00

  • Large-scale gene discovery in human airway epithelia reveals novel transcripts.

    abstract::The airway epithelium represents an important barrier between the host and the environment. It is a first site of contact with pathogens, particulates, and other stimuli, and has evolved the means to dynamically respond to these challenges. In an effort to define the transcript profile of airway epithelia, we created ...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00188.2003

    authors: Scheetz TE,Zabner J,Welsh MJ,Coco J,Eyestone Mde F,Bonaldo M,Kucaba T,Casavant TL,Soares MB,McCray PB Jr

    更新日期:2004-03-12 00:00:00

  • Iron-related transcriptomic variations in CaCo-2 cells, an in vitro model of intestinal absorptive cells.

    abstract::Regulation of iron absorption by duodenal enterocytes is essential for the maintenance of homeostasis by preventing iron deficiency or overload. Despite the identification of a number of genes implicated in iron absorption and its regulation, it is likely that further factors remain to be identified. For that purpose,...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00297.2005

    authors: Chicault C,Toutain B,Monnier A,Aubry M,Fergelot P,Le Treut A,Galibert MD,Mosser J

    更新日期:2006-06-16 00:00:00

  • Transcriptional reprogramming and ultrastructure during atrophy and recovery of mouse soleus muscle.

    abstract::This study investigated the use of the hindlimb suspension (HS) and reloading model of mice for the mapping of ultrastructural and gene expressional alterations underlying load-dependent muscular adaptations. Mice were hindlimb suspended for 7 days or kept as controls (n = 12). Soleus muscles were harvested after HS (...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00100.2004

    authors: Däpp C,Schmutz S,Hoppeler H,Flück M

    更新日期:2004-12-15 00:00:00

  • Genetic architecture of fast- and slow-twitch skeletal muscle weight in 200-day-old mice of the C57BL/6J and DBA/2J lineage.

    abstract::The aim of the study was to explore the genetic architecture influencing weight of fast- and slow-twitch skeletal muscles. The weights of the slow-twitch soleus, the mixed gastrocnemius, the fast-twitch tibialis anterior (TA), and extensor digitorum longus (EDL) muscles were 11-34% greater (P < 0.001) in 200-day-old C...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00103.2003

    authors: Lionikas A,Blizard DA,Vandenbergh DJ,Glover MG,Stout JT,Vogler GP,McClearn GE,Larsson L

    更新日期:2003-12-16 00:00:00

  • Divergent evolution of the myosin heavy chain gene family in fish and tetrapods: evidence from comparative genomic analysis.

    abstract::Myosin heavy chain genes (MYHs) are the most important functional domains of myosins, which are highly conserved throughout evolution. The human genome contains 15 MYHs, whereas the corresponding number in teleost appears to be much higher. Although teleosts comprise more than one-half of all vertebrate species, our k...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00278.2006

    authors: Ikeda D,Ono Y,Snell P,Edwards YJ,Elgar G,Watabe S

    更新日期:2007-12-19 00:00:00

  • High-fat diet caused widespread epigenomic differences on hepatic methylome in rat.

    abstract::A high-fat (HF) diet is associated with progression of liver diseases. To illustrate genome-wide landscape of DNA methylation in liver of rats fed either a control or HF diet, two enrichment-based methods, namely methyl-DNA immunoprecipitation assay with high-throughput sequencing (MeDIP-seq) and methylation-sensitive...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00110.2014

    authors: Zhang Y,Wang H,Zhou D,Moody L,Lezmi S,Chen H,Pan YX

    更新日期:2015-10-01 00:00:00

  • Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles.

    abstract::Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00210.2004

    authors: Kostrominova TY,Dow DE,Dennis RG,Miller RA,Faulkner JA

    更新日期:2005-07-14 00:00:00

  • Exercise-induced modification of the skeletal muscle transcriptome in Arabian horses.

    abstract::It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for ...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00130.2016

    authors: Ropka-Molik K,Stefaniuk-Szmukier M,Z Ukowski K,Piórkowska K,Bugno-Poniewierska M

    更新日期:2017-06-01 00:00:00

  • Transcriptional profiling of the bovine hepatic response to experimentally induced E. coli mastitis.

    abstract::The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally Escherichia coli-induced mastitis. At ...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00084.2011

    authors: Jørgensen HB,Buitenhuis B,Røntved CM,Jiang L,Ingvartsen KL,Sørensen P

    更新日期:2012-06-01 00:00:00

  • Modulation of the allergic asthma transcriptome following resiquimod treatment.

    abstract::Resiquimod is a compound belonging to the imidazoquinoline family of compounds known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. The aim of the present study was to elucidate the molecular processes tha...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00057.2009

    authors: Camateros P,Kanagaratham C,Henri J,Sladek R,Hudson TJ,Radzioch D

    更新日期:2009-08-07 00:00:00

  • Mapping blood pressure loci in (A/J x B6)F2 mice.

    abstract::Although the genetics of rare, monogenic, forms of human hypertension are fairly well defined, the genetics of the common polygenic form of human essential hypertension is only emerging. With the ability to control environmental variables, animal models have provided valuable tools with which to study blood pressure (...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00027.2003

    authors: Woo DD,Kurtz I

    更新日期:2003-11-11 00:00:00

  • Identification of new targets of Drosophila pre-mRNA adenosine deaminase.

    abstract::Adenosine deaminase acting on RNA (ADAR) in Drosophila and mammals has recently become the target of numerous investigations. It is now clear that this protein has a number of functions in the nervous system. Indeed, the mutation of ADAR in Drosophila (dADAR) results in many pathological and physiological changes, suc...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00093.2003

    authors: Xia S,Yang J,Su Y,Qian J,Ma E,Haddad GG

    更新日期:2005-01-20 00:00:00

  • Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis.

    abstract::Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) (...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00133.2003

    authors: Wu SJ,Chiang FT,Chen WJ,Liu PH,Hsu KL,Hwang JJ,Lai LP,Lin JL,Tseng CD,Tseng YZ

    更新日期:2004-04-13 00:00:00

  • Localization of a blood pressure QTL on rat chromosome 1 using Dahl rat congenic strains.

    abstract::We previously reported that markers on rat chromosome 1 are genetically linked to blood pressure in an F(2) population derived from Dahl salt hypertension-sensitive (S) and Lewis (LEW) rats. Because there was evidence for more than one blood pressure quantitative trait locus (QTL) on chromosome 1, an initial congenic ...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.1999.1.3.119

    authors: Saad Y,Garrett MR,Lee SJ,Dene H,Rapp JP

    更新日期:1999-11-11 00:00:00

  • Alternative promoter usage and alternative splicing contribute to mRNA heterogeneity of mouse monocarboxylate transporter 2.

    abstract::Expression patterns of monocarboxylate transporter 2 (MCT2) display mRNA diversity in a tissue-specific fashion. We cloned and characterized multiple mct2 5'-cDNA ends from the mouse and determined the structural organization of the mct2 gene. We found that transcription of this gene was initiated from five independen...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00192.2007

    authors: Zhang SX,Searcy TR,Wu Y,Gozal D,Wang Y

    更新日期:2007-12-19 00:00:00

  • Linkage of myostatin pathway genes with knee strength in humans.

    abstract::This study was the first to explore the potential role of the myostatin (GDF8) pathway in relation to muscle strength and estimated muscle cross-sectional area in humans using linkage analysis with a candidate gene approach. In young male sibs (n = 329) 11 polymorphic markers in or near 10 candidate genes from the myo...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00224.2003

    authors: Huygens W,Thomis MA,Peeters MW,Aerssens J,Janssen R,Vlietinck RF,Beunen G

    更新日期:2004-05-19 00:00:00

  • RNA viruses and microRNAs: challenging discoveries for the 21st century.

    abstract::RNA viruses represent the predominant cause of many clinically relevant viral diseases in humans. Among several evolutionary advantages acquired by RNA viruses, the ability to usurp host cellular machinery and evade antiviral immune responses is imperative. During the past decade, RNA interference mechanisms, especial...

    journal_title:Physiological genomics

    pub_type: 杂志文章,评审

    doi:10.1152/physiolgenomics.00112.2013

    authors: Swaminathan G,Martin-Garcia J,Navas-Martin S

    更新日期:2013-11-15 00:00:00

  • Targeted disruption of nuclear factor erythroid-derived 2-like 1 in osteoblasts reduces bone size and bone formation in mice.

    abstract::Previous in vitro studies found that nuclear factor erythroid-derived 2-like 1 (NFE2L1) was involved in mediating ascorbic acid-induced osterix expression and osteoblast differentiation via binding to the antioxidant response element of the osterix promoter. To test the role of NFE2L1 in regulating bone formation in v...

    journal_title:Physiological genomics

    pub_type: 杂志文章

    doi:10.1152/physiolgenomics.00105.2009

    authors: Kim J,Xing W,Wergedal J,Chan JY,Mohan S

    更新日期:2010-01-08 00:00:00