scholarly journals Protective effect of peroxisome proliferator-activated receptor- in regulating the early inflammation response to extended hepatectomy from a comparative transcriptomic analysis

2021 ◽  
Author(s):  
Cheng-Cheng Shi ◽  
Yang Bai ◽  
Xin Yan ◽  
Nuo Cheng ◽  
Wen-Zhi Guo ◽  
...  
Keyword(s):  
Major Hepatectomy ◽  
Expression Patterns ◽  
Regulation Mechanism ◽  
Peroxisome Proliferator ◽  
Remnant Liver ◽  
Extended Hepatectomy ◽  
Peroxisome Proliferator Activated Receptor ◽  
Module Eigengene ◽  
Molecular Profiles ◽  
Small For Size

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module and the lightcyan module were found positively correlated with not extended hepatectomy but major hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and verified the down-regulation in the remnant liver following extended hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.

Abstract 290: Proliferation of Cardiac Fibroblasts Defines Early Stages of Genetic Dilated Cardiomyopathy and Precedes Myocardial Metabolic Derangement

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Michael A Burke ◽  
Stephen Chang ◽  
Danos C Christodoulou ◽  
Joshua M Gorham ◽  
Hiroko Wakimoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibroblasts ◽  
Expression Patterns ◽  
Molecular Networks ◽  
Peroxisome Proliferator ◽  
Metabolic Derangement ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Remodeling ◽  
Ppar Signaling ◽  
Myocyte Proliferation

The complex molecular networks underpinning DCM remain poorly understood. To study distinct pathways and networks in the longitudinal development of DCM we performed RNAseq on LV tissue from mice carrying a human DCM mutation in phospholamban (PLN R9C/+ ) before phenotype onset (pre-DCM), with DCM, and during overt heart failure (HF), and also on isolated myocytes and non-myocytes from DCM hearts. PLN R9C/+ mice show progressive fibrosis (20% vs. 1% control, p=6x10 −33 ; n=3) associated with proliferation of cardiac non-myocytes (33% increase over control, p=6x10 −4 ; n=3). Consistent with this, cardiac non-myocytes have upregulated gene expression and pathways, while these are generally downregulated in myocytes. Non-myocytes were enriched in fibrosis, inflammation, and cell remodeling pathways, from pre-DCM to HF. In contrast, myocytes were enriched for metabolic pathways only with overt DCM and HF. Myocytes showed profound derangement of oxidative phosphorylation with DCM (p=2.5x10 −41 ; 44% (53/120) of pathway genes downregulated), suggesting mitochondrial dysfunction. Additionally, we detected probable inhibition of peroxisome proliferator-activated receptor (PPAR) signaling by diminished expression of pathway genes (Figure). DCM and hypertrophic remodeling was compared using RNAseq of a mouse model of HCM; similar patterns of fibrosis with myocyte metabolic dysregulation were evident despite unique differential gene expression patterns between models. DCM caused by PLN R9C/+ is associated with early non-myocyte proliferation and later myocyte metabolic derangement possibly governed by altered PPAR signaling, and is common to DCM and HCM.

scholarly journals Increasing the remnant liver volume using portal vein embolization

2010 ◽  
Vol 4 (5) ◽  
pp. 817-820
Author(s):  
Thanis Saksirinukul ◽  
Permyot Kosolbhand ◽  
Natthaporn Tanpowpong
Keyword(s):  
Portal Vein ◽  
Portal Vein Embolization ◽  
Major Hepatectomy ◽  
Liver Volume ◽  
Measurement Methods ◽  
Remnant Liver ◽  
Extended Hepatectomy ◽  
Volumetric Measurement ◽  
Common Procedure ◽  
Total Liver Volume

Abstract Background: Portal vein embolization (PVE) is a common procedure to induce hypertrophy of the remnant liver (RL) before major hepatectomy. Objective: Evaluate increased RL volume after PVE based on CT volumetric measurement. Methods: Multi-detector computed tomography (MDCT) was used to measure hepatic volumetric measurement, including total liver volume and RL volumes of pre- and post-PVE. Complications were recorded from PVE and from three-month after post-extended hepatectomy liver dysfunction. Result and conclusion: There was a 10% increase in RL volume. Mean days between CT and PVE were 20 days. No major complications from PVE were observed.

scholarly journals Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

2017 ◽  
Vol 313 (4) ◽  
pp. G313-G319 ◽  
Author(s):  
Mohammad Golriz ◽  
Sepehr Abbasi ◽  
Parham Fathi ◽  
Ali Majlesara ◽  
Thorsten Brenner ◽  
...  
Keyword(s):  
Liver Resection ◽  
Hepatic Artery ◽  
Base Excess ◽  
Jugular Vein ◽  
Liver Volume ◽  
Remnant Liver ◽  
Extended Hepatectomy ◽  
Acid Base ◽  
Jugular Veins ◽  
Small For Size

Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75, 50, and 25%, respectively). Blood gas values were measured before and after each step using four catheters inserted into the carotid artery, internal jugular vein, hepatic artery, and portal vein. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. EH correlated with reduced BE in the hepatic artery. Pco2 values increased after 75% resection in the jugular vein. In contrast, arterial Po2 increased after every resection, whereas the venous Po2 decreased slightly. There were differences in venous [Formula: see text], BE in the hepatic artery, and Pco2 in the jugular vein after 75% liver resection. Because 75% resection is the limit for SFSF, these noninvasive blood evaluations may be used to predict SFSF. Further studies with long-term follow-up are required to validate this correlation. NEW & NOTEWORTHY This is the first study to evaluate acid-base parameters in major central and hepatic vessels during stepwise liver resection. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. Extended hepatectomy correlated with reduced BE in the hepatic artery. Because 75% resection is the limit for small for size and flow syndrome (SFSF), postresection blood gas evaluations may be used to predict SFSF.

scholarly journals A meta-analysis study of gene expression datasets in mouse liver under PPARα knockout

2013 ◽  
Vol 95 (2-3) ◽  
pp. 78-88 ◽  
Author(s):  
KAN HE ◽  
ZHEN WANG ◽  
QISHAN WANG ◽  
YUCHUN PAN
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Hepatic Tissue ◽  
Marker Genes ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Microarray Datasets

SummaryGene expression profiling of peroxisome-proliferator-activated receptor α (PPARα) has been used in several studies, but there were no consistent results on gene expression patterns involved in PPARα activation in genome-wide due to different sample sizes or platforms. Here, we employed two published microarray datasets both PPARα dependent in mouse liver and applied meta-analysis on them to increase the power of the identification of differentially expressed genes and significantly enriched pathways. As a result, we have improved the concordance in identifying many biological mechanisms involved in PPARα activation. We suggest that our analysis not only leads to more identified genes by combining datasets from different resources together, but also provides some novel hepatic tissue-specific marker genes related to PPARα according to our re-analysis.

Gene expression profiling of potential PPARγ target genes in mouse aorta

2004 ◽  
Vol 18 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Henry L. Keen ◽  
Michael J. Ryan ◽  
Andreas Beyer ◽  
Satya Mathur ◽  
Todd E. Scheetz ◽  
...  
Keyword(s):  
Target Genes ◽  
Vascular Dysfunction ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Oxidoreductase Activity ◽  
Data Set ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

Diminished activity of peroxisome proliferator-activated receptor-γ (PPARγ) may play a role in the pathogenesis of hypertension and vascular dysfunction. To better understand what genes are regulated by PPARγ, an experimental data set was generated by microarray analysis, in duplicate, of pooled aortic mRNA isolated from mice treated for 21 days with a PPARγ agonist (rosiglitazone) or vehicle. Of the 12,488 probe sets present on the array (Affymetrix MG-U74Av2), 181 were differentially expressed between groups according to a statistical metric generated using Affymetrix software. A significant correlation was observed between the microarray results and real-time RT-PCR analysis of 39 of these genes. Cluster analysis revealed 3 expression patterns, 29 transcripts of moderate abundance that were decreased (−93%) to very low levels, 106 transcripts that were downregulated (−42%), and 46 transcripts that were upregulated (+70%). Functional groups that were decreased included inflammatory response (−93%, n = 6), immune response (−86%, n = 7), and cytokines (−82%, n = 7). There was an overall upregulation in the oxidoreductase activity group (+47%, n = 9). Individually, six transcripts in this group were increased (+72%), and three were decreased (−34%). Fourteen of the genes map to regions in the rat genome that have been linked to increased blood pressure, and of 142 upstream regions analyzed, sequences resembling the DNA binding site for PPARγ were identified in 101 of the differentially expressed genes.

scholarly journals Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization

Reproduction ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 537-552 ◽  
Author(s):  
Carolina Gillio-Meina ◽  
Sen Han Phang ◽  
James P Mather ◽  
Brian S Knight ◽  
Thomas G Kennedy
Keyword(s):  
Expression Patterns ◽  
Retinoid X Receptor ◽  
Early Event ◽  
Prostaglandin E ◽  
Peroxisome Proliferator ◽  
Decidual Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
Prostacyclin Receptor ◽  
Retinoid X Receptor Alpha ◽  
Prostacyclin Synthase

To determine if changes in endometrial expression of the enzymes and receptors involved in prostaglandin (PG) synthesis and action might provide insights into the PGs involved in the initiation of decidualization, ovariectomized steroid-treated rats at the equivalent of day 5 of pseudopregnancy were given a deciduogenic stimulus and killed at various times up to 32 h thereafter. The expression of PG-endoperoxide synthases (PTGS1 and PTGS2), microsomal PGE synthases (PTGES and PTGES2), cytosolic PGE synthase (PTGES3), prostacyclin synthase (PTGIS), prostacyclin receptor, peroxisome proliferator-activated receptor δ (PPARD) and retinoid x receptor α (RXRA) in endometrium was assessed by semiquantitative RT-PCR, western blot analyses and immunohistochemistry. In addition, to determine which PG is involved in mediating decidualization, we compared the ability of PGE2, stable analogues of PGI2, L165041 (an agonist of PPARD), and docasahexanoic acid (an agonist of RXRA) to increase endometrial vascular permeability (EVP, an early event in decidualization), and decidualization when infused into the uterine horns of rats sensitized for the decidual cell reaction (DCR). EVP was assessed by uterine concentrations of Evans blue 10 h after initiation of infusions. DCR was assessed by the uterine mass 5 days after the initiation of the infusions. Because enzymes associated with the synthesis of PGE2, including PTGS2, are up-regulated in response to a deciduogenic stimulus and because PGE2 was more effective than the PGI2 analogues and PPARD and RXRA agonists in increasing EVP and inducing decidualization, we suggest that PGE2 is most likely the PG involved in the initiation of decidualization in the rat.

scholarly journals Transient Expression of Interferon-Inducible p204 in the Early Stage Is Required for Adipogenesis in 3T3-L1 Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3141-3153 ◽  
Author(s):  
Jing Xiao ◽  
Bing Sun ◽  
Guo-ping Cai
Keyword(s):  
Transient Expression ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Expression Patterns ◽  
Immunofluorescence Assay ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Irreversible Damage ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

A member of the interferon-inducible p200 family of proteins, p204, has recently been reported to function in the development of many mesoderm-derived tissues, such as bone, muscle, and cartilage. However, no published study has yet investigated the role of p204 in adipogenesis. Our preliminary experiments showed that p204 can be found in 3T3-L1 preadipocytes, and its expression was up-regulated in a differentiation-dependent manner. As such, we hypothesized that p204 is associated with adipogenesis and focused on the influence of p204 on adipogenesis. In the present study, we investigated the transient elevated expression and cytoplasm-to-nucleus translocation of p204 in the early stage of adipogenesis. To determine the effect of p204 on adipogenesis, p204-siRNA and expression vector were produced for p204 suppression and overexpression, respectively. The knockdown of p204 resulted in a significantly depressed adipocyte differentiation, whereas p204 overexpression promoted adipocyte differentiation. The mRNA expression of adipogenic markers, such as peroxisome-proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding-protein (C/EBP)α, lipoprotein lipase, and adipsin, was decreased by p204 suppression and increased by p204 overexpression. A coimmunoprecipitation assay coupled with an indirect immunofluorescence assay also indicated that p204 interacted and colocalized with C/EBPδ in the nucleus. Furthermore, the knockdown of p204 disrupted the interaction between p204 and C/EBPδ and partially suppressed the PPARγ transcriptional activity by dissociating C/EBPδ with the PPARγ promoter element. Collectively, our data indicate that the transient expression of p204 in the early stage is indispensable for adipocyte differentiation. Disruption of p204 expression patterns at this stage leads to irreversible damage in fat formation.

scholarly journals Protein Profiling of Mouse Livers with Peroxisome Proliferator-Activated Receptor α Activation

2004 ◽  
Vol 24 (14) ◽  
pp. 6288-6297 ◽  
Author(s):  
Ruiyin Chu ◽  
Hanjo Lim ◽  
Laura Brumfield ◽  
Hong Liu ◽  
Chris Herring ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Acid Metabolism ◽  
Liver Tumors ◽  
Expression Patterns ◽  
Protein Profiling ◽  
Acid Decarboxylase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Proteomic Approach ◽  
Aldolase B

ABSTRACT Peroxisome proliferator-activated receptor α (PPARα) is important in the induction of cell-specific pleiotropic responses, including the development of liver tumors, when it is chronically activated by structurally diverse synthetic ligands such as Wy-14,643 or by unmetabolized endogenous ligands resulting from the disruption of the gene encoding acyl coenzyme A (CoA) oxidase (AOX). Alterations in gene expression patterns in livers with PPARα activation were delineated by using a proteomic approach to analyze liver proteins of Wy-14,643-treated and AOX−/− mice. We identified 46 differentially expressed proteins in mouse livers with PPARα activation. Up-regulated proteins, including acetyl-CoA acetyltransferase, farnesyl pyrophosphate synthase, and carnitine O-octanoyltransferase, are involved in fatty acid metabolism, whereas down-regulated proteins, including ketohexokinase, formiminotransferase-cyclodeaminase, fructose-bisphosphatase aldolase B, sarcosine dehydrogenase, and cysteine sulfinic acid decarboxylase, are involved in carbohydrate and amino acid metabolism. Among stress response and xenobiotic metabolism proteins, selenium-binding protein 2 and catalase showed a dramatic ∼18-fold decrease in expression and a modest ∼6-fold increase in expression, respectively. In addition, glycine N-methyltransferase, pyrophosphate phosphohydrolase, and protein phosphatase 1D were down-regulated with PPARα activation. These observations establish proteomic profiles reflecting a common and predictable pattern of differential protein expression in livers with PPARα activation. We conclude that livers with PPARα activation are transcriptionally geared towards fatty acid combustion.

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